Effects of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion
Effects of notoginsenoside R1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion
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DOI：
10.3748/wjg.14.29
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发表时间：
2008-01-07
影响因子：
4.3
通讯作者：
Han, Jing-Yan
中科院分区：
文献类型：
--
作者：
Chen, Wei-Xing;Wang, Fang;Han, Jing-Yan
目的：方法：结扎C57/BL小鼠肠系膜上动脉（上级SMA）15 min，造成肠缺血再灌注30 min，观察三七总皂苷R1对肠缺血再灌注（I/R）所致小鼠肝脏微循环障碍的影响。在另一组实验中，从I/R前10 min至研究结束持续输注R1（10 mg/kg/h），以研究R1对肠道I/R诱导的肝微循环障碍的影响。倒置显微镜下观察肝脏微循环，测定血管直径、红细胞流速和血窦灌注。激光共聚焦显微镜下观察白细胞的滚动和粘附。分别于再灌注30 min和60 min测定外周血乳酸脱氢酶（LDH）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）。流式细胞术检测中性粒细胞粘附分子CD 11b/CD 18的表达，血浆肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和单核细胞趋化蛋白-1（MCP-1）的表达。免疫荧光法检测肝组织中E-选择素和细胞间粘附分子-1（ICAM-1）的表达。肠I/R后，门静脉终末和中央静脉内径、红细胞流速、血窦数目减少，白细胞滚动和粘附、肝血管E-选择素表达、中性粒细胞CD 18、IL-6、MCP-1、LDH、ALT和AST升高。结论：R1可预防I/R引起的肝微循环障碍和肝细胞损伤。R1的作用与其通过抑制内皮细胞E-选择素和中性粒细胞CD 18的表达来抑制白细胞滚动和粘附有关。
AIM: To assess the effect of notoginsenoside R1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion (I/R) in mice.METHODS: The superior mesenteric artery (SMA) of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-min reperfusion. In another set of experiments, R1 was continuously infused (10 mg/kg per hour) from 10 min before I/R until the end of the investigation to study the influence of R1 on hepatic microcirculatory disturbance induced by gut I/R. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell (RBC) velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate transaminase (AST) in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in plasma were evaluated by flow cytometry. E-selectin and intercellular adhesion molecule-1 (ICAM-1) in hepatic tissue were examined by immunofluorescence.RESULTS: After gut I/R, the diameters of terminal portal venules and central veins, RBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. R1 treatment attenuated these alterations except for IL-6 and MCP-1.CONCLUSION: R1 prevents I/R-induced hepatic microcirculation disturbance and hepatocyte injury. The effect of R1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.