Original Research Open Access
Copyright ©The Author(s) 2001. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 15, 2001; 7(5): 672-677
Published online Oct 15, 2001. doi: 10.3748/wjg.v7.i5.672
Effects of extract F of red-rooted Salvia on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock-reperfusion in rats
Li-Hong Zhang, Department of Anesthesiology, Second Clinical College, China Medical University, Shenyang 110003, Liaoning Province, China.
Chang-Bai Yao, Department of General Surgery, Second Clinical College, China Medical University, Shenyang 110003, Liaoning Province, China.
He-Quan Li, Department of Pathophysiology, China medical University, Shenyang 110003, Liaoning Province, China.
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No. 3870890
Correspondence to: Li-Hong Zhang, Department of Anesthesiology, Second Clinical College, China Medical University, 36 Sanhao Street, Shenyang 110003, Liaoning Province, China. cumzhanglihong@163.net
Telephone: +86-24-24133628
Received: March 19, 2001
Revised: May 6, 2001
Accepted: June 12, 2001
Published online: October 15, 2001

Abstract

AIM: To compare the effects of extract F of red-rooted Salvia (EFRRS) on mucosal lesions of gastric corpus and antrum induced by hemorr hagic shock and reperfusion in rats.

METHODS: The rats were subject to hemorrhagic shock and followed by reperfusion, and were divided randomly into two groups. Group 1 received saline, and group 2 received EFRRS intravenously. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesional area in the corpus or antrum. The degree of gastric mucosal lesions (DGML) was catalogued grade 0, 1, 2 and 3. The concentrations of prostaglandins (PGs) were measured by radioimmunoassay. The concentration of MDA was measured according to the procedures of Asakawa. The activity of SOD was measured by the biochemical way. The growth rates or inhibitory rates of above-mentioned parametes were calculated.

RESULTS: As compared with IGML (%), grade 3 damage (%) and MDA content (nmol/g tissue) of gastric antrum which were respectively 7.96 ± 0.59, 34.86 ± 4.96 and 156.98 ± 16.12, those of gastric corpus which were respectively 23.18 ± 6.82, 58.44 ± 9.07 and 230.56 ± 19.37 increased markedly (P ＜ 0.01), whereas the grade 0 damage, grade 1 damage, the concentrations of PGE2 and PGI2 (pg/mg tissue), the ratio of PGI2/TXA2 and the activity of SOD (U/g tissue) of corpus which were respectively 3.01 ± 1.01, 8.35 ± 1.95, 540.48 ± 182.78, 714.38 ± 123.74, 17.38 ± 5.93 and 134.29F13.35 were markedly lower than those of antrum which were respectively 13.92 ± 2.25, 26.78 ± 6.06, 2218.56 ± 433.12, 2531.76 ± 492.35, 43.46 ± 8.51 and 187.45 ± 17.67 (P ＜ 0.01) after hemorrhagic shock and reperfusion. After intravenous EFRRS, the growth rates (%) of grade 0 damage, grade 1 damage, the concentrations of PGE2 and PGI2, the ratio of PGI2/TXA2 and the activity of SOD of corpus which were respectively 632.56, 308.62, 40.75, 74.75, 92.29 and 122.25 were higher than those in antrum which were respectively 104.89, 58.40, 11.12, 56.58, 30.65 and 82.64, whereas the inhibitory rates (%) of IGML, grade 3 damage and MDA content of gastric corpus were 82.93, 65.32 and 59.09, being higher than those of gastric antrum which were 76.64, 53.18 and 42.37.

CONCLUSION: After hemorrhagic shock-reperfusion, the gastric mucosal lesions in the corpus were more severe than those in the antrum, which were related not only to the different distribution of endogenous PGs in the mucosa, but also to the different ability of anti-oxidation of the mucosa. The protective effect of EFRRS on the gastric mucosa in the corpus was more evident than that in the antrum, which was related to higher growth degree of PGs contents and anti-oxitative ability in gastric corpus after administration of EFRRS.

Key Words: plant extracts/pharmacology; gastric mucosa/pathology; shock hemorrhagic; reperfusion; hydroxyl radical

INTRODUCTION

More and more stress has been put on gastric mucosal reperfusional injury. Though scholars both at home and abroad have performed plenty of researches on it, there has been no satisfying method or drug yet[1-5]. Red-rooted Salvia is the traditional Chinese medicine for accelerating blood circulation and ameliorating congestion, and its pharmacological effect is very extensive. Resources of red-rooted Salvia in China is sufficient. It has been evidenced that the proportion of red-rooted Salvia dissolving in water can treat acute or chronic gastric mucosal lesions, and has protective effect on gastric mucosa. Extract F of red-rooted Salvia (EFRRS) is extracted from the proportion of red-rooted Salvia dissolving in water[6-11]. Because Prostaglandins (PGs) and oxygen free radical (OFR) play important roles in reperfusional injury[12-18], the present experiment was AIMed at studying the endogenous PGs and the anti-oxidation of the gastric corpus and the antrum, and comparing their ability to resist the lesions induced by hemorrhagic shock-reperfusion in rats and the protective effect of EFRRS on the gastric corpus and the antrum.

MATERIALS AND METHODS
Drug

EFRRS was extracted from red-rooted Salvia solution provided by Chemical Assay Center of China Medical University using column chromatography.

Animal models

Male Wistar rats, weighing 260 g-300 g, were fasted overnight. The rats were anesthetized intraperitoneally with 5 mg ± 100 g¯¹ of 20% Urethane. Tracheostomy was performed and PE-250 tubing was inserted into the trachea to maintain an open airway. Then open the abdomen and lavage the gastric lumen gently with warm saline. The right carotid artery was cannulated using a polyethylene tube to monitor the blood pressure. The femoral artery was canulated for withdrawing the blood and reinfused the shed blood. After the blood pressure was stabilized, normal saline or EFRRS (1 g·100 gwt¯¹) was administered for 25 min via a tail vein (0.03 mL•min¯¹). One mL of 0.1 mol/L HCl per 100 g body wt was then instilled into the stomach via the gastric tube, five min after the intragastric instillation of HCL, blood was withdrawn from the femoral artery. The mean arterial blood pressure fell to 2.67 kPa-4.0 kPa and was maintained at that level for 20 min. The shed blood was then reinfused, and 20 min later the rats were sacrificed[19]. Rats were allocated into two groups. Group 1 (n = 9) received NS via the tail vein, and group 2 (n = 7) received EFRRS (1 g·100 gwt¯¹) via the tail vein.

Index of gastric mucosal lesions (IGML) and inhibitory rate (IR) of IGML

The corpus and antrum lesional areas were measured in square millimeters. IGML was expressed as the percentage of lesional area in the corpus or antrum[20]. IR was calculated by the following formula.

IR = (Difference of mean value of lesional areas between the two groups)/(Mean value of lesional area in group 1) × 100%

Depth of gastric mucosal lesions (DGML), growth rate (GR) and IR of DGML

After meaursing the lesional areas, the samples for light microscopy (LM) and scanning electron microscopy (SEM) were taken from the proximal anterior wall of the corpus or the middle of the antrum. The samples analyzed by LM were evaluated as follows[21]. The damage was graded as 0, 1, 2 and 3. Grade 0 was defined as normal intact surface mucous cells with intact gastric pits and glands. Grade 1: Surface mucous cells were vacuolated with pyknotic nuclei. Some exfoliation was present. Grade 2: In addition to the above changes, the cells lining the gastric pits were also disrupted and exfoliated. Grade 3: Cell destruction extended into the gastric glands (Figure 1, Figure 2, Figure 3, Figure 4 Figure 5, Figure 6). Samples analyzed by SEM were evaluated as follows[22]. Grade 0: The mucosa showed closely packed, polygonal surface mucous cells and narrow openings to the gastric pits. Grade 1: Surface cells were flattened with irregular shape, and gaps between individual cells. Grade 2: The basal lamina was exposed and was largely devoid of surface mucous cells, but still showed continuity, wide openings to the gastric pits were visible. The picture resembled that of a honeycomb. Grade 3: Most of the basal lamina were disrupted, and only a portion being still intact. Regular surface cells were no longer present (Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12). A close correlation between LM and SEM grading was found (r = 0.846, P ＜ 0.01). The percentage of damage of each grade was calculated in each group. The METHODS to calculate the GR or IR of DGML were the same as that of IR of the lesional area.

Figure 1
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Figure 1 Grade 1 damage in gastric corpus and antrum. LM × 330. In grade 1 damage, surface mucous cells were damaged.
Figure 2
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Figure 2 Grade 1 damage in gastric corpus and antrum. LM × 330. In grade 1 damage, surface mucous cells were damaged.
Figure 3
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Figure 3 Grade 2 damage in gastric corpus and antrum. LM × 330. In grade 2 damage, the cells kining the gastric pits were also disrupted.
Figure 4
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Figure 4 Grade 2 damage in gastric corpus and antrum. LM × 330. In grade 2 damage, the cells kining the gastric pits were also disrupted.
Figure 5
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Figure 5 Grade 3 damage in gastric corpus and antrum. LM × 330. In grade 3 damage, cell destruction extended into the gastric glands.
Figure 6
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Figure 6 Grade 3 damage in gastric corpus and antrum. LM × 330. In grade 3 damage, cell destruction extended into the gastric glands.
Figure 7
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Figure 7 Grade 1 damage in gastric corpus. SEM × 1500.
Figure 8
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Figure 8 Grade 2 damage in gastric corpus. SEM × 1500.
Figure 9
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Figure 9 Grade 3 damage in gastric corpus. SEM × 1500.
Figure 10
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Figure 10 Grade 1 damage in gastric antrum. SEM × 1500. In grade 1 damage, surface cells were of irregular shape, and gaps between indiv idual cells were present.
Figure 11
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Figure 11 Grade 2 damage in gastric antrum. SEM × 1500. In grade 2 damage, the basal lamina was exposed, but still showed continuity. Wide openings to the gastric pits were visible.
Figure 12
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Figure 12 Grade 3 damage in gastric antrum. SEM × 1500. In grade 3 damage, most of the basal lamina was disrupted, Regular surface cells were no longer present.
PGs contents and GRs of PGs

Prostaglandin E2 (PGE2), 6-keto-PGF1α (6-keto-PGF1α: 6-keto is the metabolite of PGI2), and TXB2 (metabolite of TXA2) boxes were provided by Biochemistry Laboratory of Liberal Army General Hospital, and their concentrations were assayed by using radiommunoassay. GRs of PGs were calculated in the same way as that of IR of the lesional area.

MDA content and IR of MDA

Malondialdehyde (MDA) is the final metabolism product of OFR. It can be measured by the way of Asakawa[23]. IR of MDA was calculated in the same way as that of IR of lesional area.

SOD activity and GR of SOD

Superoxide dimutase (SOD) was measured according to the biochemical method[24]. GR of SOD was calculated in the same way as that of IR of lesional area.

In all experiments, the date was represented by the mean value ± standard error, and analyzed by paired t test. P value of ＜ 0.05 was considered significant.

RESULTS
Comparison of IGML and its IRs between the gastric corpus and antrum

The results are shown in Table 1. After hemorrhagic shock-reperfusion, IGML in the corpus was much higher than that in the antrum (P ＜ 0.01). As compared with that in the corpus, IR in the antrum was lower after administration of EFRRS.

Table 1 IGML and its IR in gastric corpus and antrum (%, mean ± SD).
IGMLIR
Group 1 (n = 9)
Corpus23.18 ± 6.82
Antrum7.96 ± 0.59b
Group 2 (n = 7)
Corpus4.42 ± 1.39a82.93
Antrum1.62 ± 0.37a76.64
bP ＜ 0.01, vs corpus;
aP ＜ 0.01, vs group 1.
Comparison of DGML, and its IRs and GRs between the gastric corpus and antrum

The results are shown in Table 2. As compared with those in the corpus, grade 0 and 1 damages in the antrum were much increased (P ＜ 0.01), and grade 3 damage markedly decreased (P ＜ 0.01) after hemorrhagic shock-reperfusion. After administration of EFRRS, the GR of grade 0 and 1 damage and the IR of grade 3 damage in the antrum were much less than those in the corpus.

Table 2 DGML and its IR or GR in the gastric corpus and antrum (%, mean ± SD).
DGML
0GR1GR2IR3IR
Group 1 (n = 7)
Corpus3.01 ± 1.018.35 ± 1.9531.32 ± 4.4958.44 ± 9.07
Antrum13.92 ± 2.25b26.78 ± 6.06b25.98 ± 8.3234.86 ± 4.96b
Group 2 (n = 6)
Corpus22.05 ± 5.96a632.5634.12 ± 8.12a308.6225.96 ± 10.0417.1120.32 ± 6.95a65.32
Antrum28.52 ± 8.12a104.8942.42 ± 8.58a58.4014.03 ± 3.13a45.9816.32 ± 4.05a53.18
bP ＜ 0.01, vs corpus;
aP ＜ 0.01, vs group 1.
Comparison of the concentrations of PGE2, 6-keto and TXB2, the ratio of 6-keto/TXB2 and their GRs between the gastric corpus and antrum

In Table 3, higher PGE2 and 6-keto levels and 6-keto/TXB2 ratio were found in the antrum compared with those in the corpus after hemorrhagic shock-reperfusion (P ＜ 0.01), and the GRs of PGE2, 6-keto and 6-keto/TXB2 in the corpus were higher than those in the antrum after administration of EFRRS.

Table 3 PGs contents (pg/mg tissue), and their GRs in the gastric corpus and antrum (%, mean ± SD).
GroupPGE2GR6-ketoGRTXB26-Keto/TXB2GR
Group 1 (n = 6)
Corpus540.48 ± 182.78714.38 ± 123.7458.28 ± 6.7417.38 ± 5.93
Antrum2218.56 ± 433.12b2531.76 ± 492.35b62.49 ± 9.5143.46 ± 8.51b
Group 2 (n = 6)
Corpus759.77 ± 192.00aa40.751248.37 ± 158.54a74.7545.37 ± 7.54aa33.42 ± 9.24a92.29
Antrum2465.17 ± 480.3611.122698.31 ± 526.7156.5850.02 ± 7.50a56.78 ± 5.45a30.65
bP ＜ 0.01, vs corpus;
aP ＜ 0.01, vs group 1;
aaP ＜ 0.05, vs group 1.
Comparison of MDA content, IR of MDA, SOD activity and GR of SOD between the gastric corpus and antrum

In Table 4, higher SOD activity and lower MDA level were found in the antrum compared with those in the corpus after hemorrhagic shock-reperfusion (P ＜ 0.01), and the GR of SOD and IR of MDA were higher in corpus than those in antrum after administration of EFRRS.

Table 4 MDA content (nmol/g tissue), SOD activity (U/g tissue), IR of MDA and GR of SOD in the gastric corpus and antrum (%, mean ± SD).
GroupMDAIRSODGR
Group 1 (n = 6)
Corpus230.56 ± 19.37134.29 ± 13.35
Antrum156.98 ± 16.12b187.45 ± 17.67b
Group 2 (n = 6)
Corpus94.32 ± 11.32a59.09298.47 ± 20.12a122.25
Antrum90.46 ± 12.45a42.37342.35 ± 26.58a82.64
bP ＜ 0.01, vs corpus;
aP ＜ 0.01, vs group 1.
DISCUSSION

Reperfusion after hemorrhagic shock can lead to multiple organ damage, i.e. reperfusional injury. The gastric lesions include stress ulcer, hemorrhage, necrosis, or perforation[25-28]. The present study showed that the area and depth of gastric mucosal lesions caused by hemorrhagic shock-reperfusion in the gastric corpus of rats were more severe than those in the antrum. This indicated that there were differences in resistance in gastric mucosa of the corpus and the antrum, which was probably related to differences in gastric mucosal blood flow, energy metabolism and the capacity to dispose the influxing hydrogen ion, but most propably was related with the different distribution of endogenous PGs and the different ability of anti-oxidation[29-33]. The present study also showed that the protective role of EFRRS was different in the gastric corpus and the antrum, EFRRS possessed more powerful capability to reduce the area of lesions and to lighten the extent of lesions in corpus than those in the antrum, indicating EFRRS had potential protective effect on the corpus mucosa, which was related to the higher changes of PGs and OFR in the corpus caused by EFRRS.

It was generally thought that gastric mucosa was affected by both injury factors as gastric acid and pepsin and protective factors as PGs and gastric mucus. Large quantities of PGs were found in the gastric mucosa. Numerous studies have doc umented that PGs possessed potent cytoprotective action. PGE2 could obviously inhibit the secretion of basal gastric acid and acid stimulated by histamine, pentagastrin and food in dogs and humans. In addition, PGE2 could increase the gastric mucus layer. PGE2 and PGI2 could dilate the blood vessel, increase the blood flow and carbohydrate secretion, and enhance the resistibility of gastric mucosa to injury. PGs could also lengthen the life span of epithelia and thick en the mucosa layer[34-37]. In many physiological and pathophysiologic al conditions, PGI2 has protective effect on gastric mucosa. On the contrary, TXA2may aggravate the gastric mucosal injury[38,39]. The present findings showed the PGE2 and PGI2 contents and PGI2/TXA2ratio in the antrum were markedly higher than those in the corpus after hemorrhagic shock-reperfusion, showing gastric antrum was more resistant than gastric corpus. Arakawa[40] found PGE2 levels in the gastric corpus were significantly lower than that in the antrum, and drug like indomethacin could easily damage the mucosa of gastric corpus. He thought that the concentration of endogenous PGE2 decided the defensive ability of gastric mucosa. The present study also showed that PGE2and 6-keto levels and 6-keto/TXB2 ratio in the antrum and the corpus both increased after administration of EFRRS, but the GRs of PGE2, 6-keto and 6-keto/TXB2 in corpus were higher than those in antrum, demonstrating the reinforcement of defensive ability of gastric corpus was more powerful after administration of EFRRS.

OFR played an important role in reperfusional injury. OFR caused lipid peroxidation (LPO) of polyunsaturated fatty acid of biomembrane, which resulted in the impairment of metabolism and function of cells, even the death of cells. Plenty of OFRs could lead to irreversible damage of gastric mucosa, because they could cause intracellular calcium overload besides of extensive LPO of tissues and cells[41-47]. OFR was produced by the system of enzyme and no-enzyme. Malondialdehyde (MDA) is the metabolite of LPO of OFR, and may reflect the degree of cells attacked by OFR, therefore MDA is usually an marker to monitor OFR. Superoxide dismutase (SOD) can clear superoxide anion, and may reflect the ability of scavenging system of free radical. Under normal conditions, OFR could be promptly cleared by the body. Only when the production of OFR markedly increased, or the ability of scavenging OFR much decreased, tissues were injured[48,49]. The study showed that there were higher SOD activity and lower MDA level in the antrum compared with those in corpus after hemorrhagic shock-reperfusion, so that the ability of anti-oxidation was more powerful in gastric antrum, and the reperfusional injury was easier in gastric corpus. This study also showed that the activity of SOD and the concentration of MDA decreased in the antrum and the corpus after administration of EFRRS, but the GR of SOD and IR of MDA in corpus were higher than those in antrum, demonstrating reinforcement of anti-oxidation of gastric corpus was more powerful after administration of EFRRS. The increase of SOD could accelerate the clearance of OFR to protect cell from the attact of OFR, while the decrease of OFR made cells produce more SOD, and clear more OFRs to form good cycle possessing the role of protective gastric mucosa.

It had been demonstrated in our previous studies[50-54], that EFRRS could increase the PGs contents, decrease the production of OFRs, and had calcium block effect, which resulted in some effects against gastric mucosal lesions induced by hemorrhagic shock-reperfusion. The present study discussed the mechanisms that the gastric injury in the corpus was easier after hemorrhagic shock-reperfusion, and the causes that the protective effects of EFRRS against gastric mucosal injury was more powerful in the corpus through both PGs contents and OFR system. This made the researches of reperfusional injury of gastric mucosa and the protective effects of EFRRS perform more profoundly and detailedly.

Footnotes

Edited by Wu XN

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