丹参多酚酸盐对小鼠肝脏缺血再灌注后肺损伤的保护作用

摘要

Objective To evaluate the protective effect of salvianolate on lung injury induced by hepatic ischemia reperfusion (IR) injury in mice and its underlying mechanisms. Methods A hepatic IR model of mice was reproduced, and 24 animals were assigned into 3U, groups (8 each) : sham operation (SO) group, control group and salvianolate (SV) group. Just before ischemia induction, animals in SV group received salvianolate injection at a dose of 60 mg/kg via tail vein, while in control group the mice received normal saline with an equal volume, and in SO group the mice received the same operation as in SV group but without producing liver ischemia Four hours after reperfusion, the serum, liver and lung tissue were collected. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum were detected and the histological changes in liver and lung were examined. The wet-to-dry weight ratio of pulmonary tissue was measured. The contents of tumor necrosis factor a (TNF-α), interleukin (IL)-6, IL-1β and IL-10 in bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay (EL1SA), and the relative mRNA levels of TNF-a, IL-6, IL-1β and IL-10 in pulmonary tissue were analyzed by real-time reverse transcription PCR (RT-PCR). The activaty of transcription factor NF-κB was measured with Western blotting analysis. Results No significant pathologic change was found in mice of SO group. Compared with the mice in control group, those in SV group exhibited lower levels of ALT and AST ( P<0. 01), lighter histological changes in liver and lung ( P<0. 05) , lower levels of wet-to-dry weight ratio of lung tissue ( P<0. 05), lower expression levels of TNF-a, IL-6, IL-1β and IL-10 in BALF and lung tissue (P<0. 05 or P<0. 01). Further examination demonstrated that the activity of NF-kB in SV group was significantly down-regulated as compared with that in control group. Conclusion Salvianolate can attenuate lung injury induced by hepatic IR in mice, the mechanism may inclade inhibition of the release of pulmonary inflammatory mediators and activation of the inflammatory signal pathway.%目的 研究丹参多酚酸盐对小鼠肝脏缺血再灌注后肺损伤的保护作用及其机制.方法 24只C57BL/6小鼠随机分为假手术组、对照组和丹参多酚酸盐组,每组8只.假手术组小鼠仅接受麻醉、开腹及关腹操作；丹参多酚酸盐组及对照组小鼠建立肝脏90min缺血再灌注模型,缺血前丹参多酚酸盐组小鼠经尾静脉注射丹参多酚酸盐60mg/kg,对照组小鼠经尾静脉注射等量生理盐水.再灌注4h后,检测各组小鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平及肝、肺组织形态学变化,测定肺组织湿/干重比,酶联免疫吸附试验(ELISA)及荧光定量PCR检测肺泡灌洗液及肺组织内肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-1β、IL-10表达水平,蛋白印迹法检测肺组织内核因子(NF)-κB亚单位P65磷酸化水平.结果 假手术组无明显病理性变化.与对照组比较,丹参多酚酸盐组小鼠血清ALT、AST水平明显降低(P＜0.01),肝脏、肺脏损伤明显改善(P＜0.05),肺组织湿/干重比明显降低(P＜0.05),肺泡灌洗液及肺组织内TNF-α、IL-6、IL-1β、IL-10的表达明显降低(P＜0.05或P＜0.01),转录因子NF-kB活化程度明显减弱.结论 丹参多酚酸盐能够减轻小鼠肝缺血再灌注后肺损伤,其机制可能与抑制肺组织内炎症介质释放及炎症信号通路活化有关.