Intestinal endotoxemia plays a central role in development of hepatopulmonary syndrome in a cirrhotic rat model induced by multiple pathogenic factors

doi:10.3748/wjg.v13.i47.6385

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Dec 21, 2007 (publication date) through Jan 3, 2025

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Research

World J Gastroenterol. Dec 21, 2007; 13(47): 6385-6395
Published online Dec 21, 2007. doi: 10.3748/wjg.v13.i47.6385

Table 1 Levels of endotoxin, TNF-α, ALT and MDA in plasma and PVP (mean ± SD, n = 6)

Groups	Endotoxin (Eu/mL)	TNF-α (ng/mL)	ALT (u/L)	MDA (nmol/mL)	PVP (H₂O cm)
Normal	0.09 ± 0.03	0.53 ± 0.16	5.85 ± 2.24	0.06 ± 0.03	10.31 ± 1.16
4th wk	0.19 ± 0.03^a	1.37 ± 0.35^a	56.24 ± 14.73^a	0.10 ± 0.05	17.54 ± 1.84^a
6th wk	0.24 ± 0.04^a	1.68 ± 0.23^a	53.50 ± 22.10^a	0.18 ± 0.03^a^c	15.44 ± 3.11^a^c
8th wk	0.31 ± 0.08^a^e	2.42 ± 0.38^a^e	219.10 ± 17.37^a^e	0.26 ± 0.06^a^e	18.38 ± 2.53^a^e

^aP < 0.05 vs normal group;

^cP < 0.05 vs 4th wk group;

^eP < 0.05 vs 6th wk group.

Table 2 Correlation analysis (n = 6)

Groups	r	P
LPS vs quantities of pulmonary capillaries	0.626	< 0.001
TNF-αvs quantities of pulmonary capillaries	0.644	< 0.001
ALT vs quantities of pulmonary capillaries	0.556	< 0.01
MDA vs quantities of pulmonary capillaries	0.691	< 0.0002
CO vs quantities of pulmonary capillaries	0.432	< 0.01
NO vs quantities of pulmonary capillaries	0.725	< 0.0001

Table 3 Changes of cell numbers in bronchoalveolar lavage fluid (mean ± SD, n = 6)

Groups	Total cell numbers (/μL)	Macrophages (/μL)	Ratio of macrophage/ total cell numbers
Normal control	582.7 ± 74.5	184.1 ± 5.4	0.32 ± 0.05
8th wk	619.2 ± 116.5	310.8 ± 27.5^a	0.51 ± 0.06^a

^aP < 0.05 vs normal control group.

Table 4 Levels of NO2-/NO3-, expression of eNOS and iNOS in lung (mean ± SD, n = 6)

Groups	NO₂^-/NO₃^- (μmol/g protein)	eNOS (IOD)	iNOS (IOD)
Normal control	3.6 ± 1.7	2385.6 ± 752.4	4214.8 ± 1783.7
4th wk	12.6 ± 3.7^a	6448.9 ± 922.7^a	8498.7 ± 2703.7^a
6th wk	18.9 ± 5.5^a^c	8008.9 ± 2812.7^a	12831.6 ± 4901.2^a^c
8th wk	26.9 ± 6.4^a^e	14704.7 ± 5779.9^a^e	19173.4 ± 2401.2^a^e

^aP < 0.05 vs normal group;

^cP < 0.05 vs 4th wk group;

^eP < 0.05 vs 6th wk group.

Table 5 Levels of eNOS and iNOS mRNA expression in lung (mean ± SD, n = 6)

Groups	eNOS	iNOS
Normal control	0.62 ± 0.07	0.22 ± 0.01
4th wk	0.65 ± 0.08^a	0.98 ± 0.03^a
6th wk	0.68 ± 0.07^a	1.23 ± 0.03^a^c
8th wk	0.75 ± 0.08^a^e	1.46 ± 0.05^a^e

^aP < 0.05 vs normal group;

^cP < 0.05 vs 4th wk group;

^eP < 0.05 vs 6th wk group.

Table 6 Analysis of correlation (n = 6)

Pairs	r	P value
Plasma endotoxin vs eNOS protein	0.6348	P < 0.01
Plasma endotoxin vs eNOS mRNA	0.7490	P < 0.01
Plasma endotoxin vs iNOS protein	0.5710	P < 0.01
Plasma endotoxin vs iNOS mRNA	0.8980	P < 0.01
Plasma TNF-αvs eNOS protein	0.8354	P < 0.01
Plasma TNF-αvs iNOS protein	0.8538	P < 0.01

Table 7 Changes of COHb and HO-1 protein in lung (mean ± SD, n = 6)

Groups	COHb (mg/g protein)	HO-1 protein (IOD)
Normal Control	0.13 ± 0.06	1515.18 ± 981.50
4th wk	0.27 ± 0.06^a	7391.47 ± 674.97^a
6th wk	0.29 ± 0.06^a	11157.03 ± 6093.39^a
8th wk	0.43 ± 0.98^a^e	24867.59 ± 11054.95^a^e

^aP < 0.05 vs normal group;

^eP < 0.05 vs 6th wk group.

Table 8 Correlation analysis (n = 6)

Groups	r	P
LPS vs COHb	0.876	< 0.01
LPS vs HO-1	0.802	< 0.01
TNF-αvs COHb	0.755	< 0.01
TNF-αvs HO-1	0.796	< 0.05

Table 9 Effect of L-NAME and AG on HO-1 expression (mean ± SD, n = 6; IOD)

Groups	6th wk	8th wk
Cirrhotic control	11157.03 ± 6093.39	24867.59 ± 11054.95
L-NAME + cirrhosis	3455.13 ± 1370.03^a	11063.48 ± 426.48^a
AG + cirrhosis	2286.59 ± 6181.20^a	9828.32 ± 799.51^a

^aP < 0.05 vs cirrhotic control group.

Table 10 Specific effect of ZnPP on expression of eNOS and iNOS (mean ± SD, n = 6)

Groups	eNOS (IOD)	iNOS (IOD)
6th wk cirrhotic control	13206.7 ± 8490.9	9401.1 ± 691.9
6th wk ZnPP	2025.7 ± 6097.1^a	3500.3 ± 237.4^a
8th wk cirrhotic control	21198.1 ± 11865.3	26419.8 ± 3560.5
8th wk ZnPP	2406.3 ± 9117.9^a	3522.8 ± 356.5^a

^aP < 0.05 vs cirrhotic control group.

Citation: Zhang HY, Han DW, Su AR, Zhang LT, Zhao ZF, Ji JQ, Li BH, Ji C. Intestinal endotoxemia plays a central role in development of hepatopulmonary syndrome in a cirrhotic rat model induced by multiple pathogenic factors. World J Gastroenterol 2007; 13(47): 6385-6395
URL: https://www.wjgnet.com/1007-9327/full/v13/i47/6385.htm
DOI: https://dx.doi.org/10.3748/wjg.v13.i47.6385