Original Article
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World J Gastroenterol. Nov 14, 2010; 16(42): 5306-5316
Published online Nov 14, 2010. doi: 10.3748/wjg.v16.i42.5306
Total salvianolic acid improves ischemia-reperfusion-induced microcirculatory disturbance in rat mesentery
Ming-Xia Wang, Yu-Ying Liu, Bai-He Hu, Xiao-Hong Wei, Xin Chang, Kai Sun, Jing-Yu Fan, Fu-Long Liao, Chuan-She Wang, Jun Zheng, Jing-Yan Han
Ming-Xia Wang, Yu-Ying Liu, Bai-He Hu, Xiao-Hong Wei, Xin Chang, Kai Sun, Jing-Yu Fan, Fu-Long Liao, Chuan-She Wang, Jun Zheng, Jing-Yan Han, Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing 100191, China
Ming-Xia Wang, Jun Zheng, Department of Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
Chuan-She Wang, Jing-Yan Han, Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing 100191, China
Author contributions: Wang MX performed the research, analyzed the data and wrote the paper; Liu YY, Hu BH, Wei XH, Chang X, Sun K, Zheng J and Wang CS performed the research and analyzed the data; Han JY designed the research; Wang MX, Fan JY, Liao FL and Han JY wrote the paper.
Supported by Production of New Medicine Program of Ministry of Science and Technology of the People’s Republic of China, No. 2008ZX09401
Correspondence to: Jing-Yan Han, MD, PhD, Professor, Chairman, Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China. hanjingyan@bjmu.edu.cn
Telephone: +86-10-82802862 Fax: +86-10-82802996
Received: April 23, 2010
Revised: June 25, 2010
Accepted: July 2, 2010
Published online: November 14, 2010
Abstract

AIM: To investigate the effect of total salvianolic acid (TSA) on ischemia-reperfusion (I/R)-induced rat mesenteric microcirculatory dysfunctions.

METHODS: Male Wistar rats were randomly distributed into 5 groups (n = 6 each): Sham group and I/R group (infused with saline), TSA group, TSA + I/R group and I/R + TSA group (infused with TSA, 5 mg/kg per hour). Mesenteric I/R were conducted by a ligation of the mesenteric artery and vein (10 min) and subsequent release of the occlusion. TSA was continuously infused either starting from 10 min before the ischemia or 10 min after reperfusion. Changes in mesenteric microcirculatory variables, including diameter of venule, velocity of red blood cells in venule, leukocyte adhesion, free radicals released from venule, albumin leakage and mast cell degranulation, were observed through an inverted intravital microscope. Meanwhile, the expression of adhesion molecules CD11b/CD18 on neutrophils was evaluated by flow cytometry. Ultrastructural evidence of mesenteric venules damage was assessed after microcirculation observation.

RESULTS: I/R led to multiple responses in mesenteric post-capillary venules, including a significant increase in the adhesion of leukocytes, production of oxygen radicals in the venular wall, albumin efflux and enhanced mast cell degranulation in vivo. All the I/R-induced manifestations were significantly reduced by pre- or post-treatment with TSA, with the exception that the I/R-induced increase in mast cell degranulation was inhibited only by pre-treatment with TSA. Moreover, pre- or post-treatment with TSA significantly attenuated the expression of CD11b/CD18 on neutrophils, reducing the increase in the number of caveolae in the endothelial cells of mesentery post-capillary venules induced by I/R.

CONCLUSION: The results demonstrated that TSA protects from and ameliorates the microcirculation disturbance induced by I/R, which was associated with TSA inhibiting the production of oxygen-free radicals in the venular wall and the expression of CD11b/CD18 on neutrophils.

Keywords: Salvia miltiorrhiza; Leukocyte adherence; Oxygen-free radicals; Albumin leakage; Ischemia-reperfusion