Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing 100191, China.
World J Gastroenterol. 2010 Nov 14;16(42):5306-16. doi: 10.3748/wjg.v16.i42.5306.
To investigate the effect of total salvianolic acid (TSA) on ischemia-reperfusion (I/R)-induced rat mesenteric microcirculatory dysfunctions.
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.
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.
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.
探讨总丹参酸（TSA）对缺血再灌注（I/R）诱导的大鼠肠系膜微循环功能障碍的影响。
雄性 Wistar 大鼠随机分为 5 组（每组 6 只）：假手术组和 I/R 组（输注生理盐水）、TSA 组、TSA+I/R 组和 I/R+TSA 组（输注 TSA，5mg/kg/h）。肠系膜 I/R 通过结扎肠系膜动静脉（10min）和随后解除闭塞来实现。TSA 从缺血前 10min 开始或再灌注后 10min 开始持续输注。通过倒置活体显微镜观察肠系膜微循变量的变化，包括小静脉直径、小静脉中红细胞速度、白细胞黏附、小静脉释放自由基、白蛋白渗漏和肥大细胞脱颗粒。同时，通过流式细胞术评估中性粒细胞表面黏附分子 CD11b/CD18 的表达。在观察微循环后评估肠系膜小静脉损伤的超微结构证据。
I/R 导致肠系膜后毛细血管小静脉产生多种反应，包括白细胞黏附显著增加、小静脉壁产生氧自由基、白蛋白漏出和体内增强肥大细胞脱颗粒。所有 I/R 诱导的表现均通过 TSA 的预处理或后处理显著降低，除了 I/R 诱导的肥大细胞脱颗粒增加仅被 TSA 的预处理抑制。此外，TSA 的预处理或后处理显著减轻了中性粒细胞表面 CD11b/CD18 的表达，减轻了 I/R 诱导的肠系膜后毛细血管小静脉内皮细胞中 caveolae 数量的增加。
结果表明，TSA 可防止和改善 I/R 引起的微循环障碍，这与 TSA 抑制小静脉壁氧自由基的产生和中性粒细胞表面 CD11b/CD18 的表达有关。
