姜黄素对肠缺血再灌注致肝损伤的保护作用

Protective effect of curcumin on liver against intestinal ischemia/reperfusion injury

目的探讨姜黄素(Curcumin)对肠缺血再灌注(I/R)致肝损伤的保护作用。方法 21只KM小鼠随机分为3组:假手术组、肠缺血45min再灌注24h的损伤组和姜黄素治疗组。损伤组和治疗组构建肠缺血再灌注小鼠模型,分别在再灌注同时腹腔注射0.3ml PVP-K30溶剂和姜黄素应用液(2.5mg/ml),6h后再次给药。术后24h全部处死,采用常规苏木精-伊红(HE)染色观察小肠和肝脏病理学变化,检测肝脏组织中丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)、一氧化氮(NO)的动态表达水平,Western blot检测肝脏中胞浆性磷脂酶A2(cPLA2)、磷酸化胞浆性磷脂酶A2(p-cPLA2)、环氧化酶-2(COX-2)和β-肌动蛋白(β-actin)的表达水平。结果观察小肠和肝脏病理损伤程度,使用Chiu′小肠组织损伤评价标准显示治疗组低于损伤组(P<0.01);ALT水平治疗组明显低于损伤组(P<0.05),NO水平较损伤组显著升高(P<0.05);LDH水平治疗组与损伤组无差异(P>0.05);Western blot显示肝脏中p-cPLA2和COX-2表达水平损伤组增高(P<0.01),治疗组相比于损伤组表达水平下降(P<0.01),而cPLA2和β-actin无明显变化。结论姜黄素对小鼠肠缺血再灌注造成的肝脏损伤有明显改善作用,可能与提高肝脏抗氧化损伤能力、调节某些炎症因子表达有关。

Objective To study the protective effect of curcumin on liver against intestinal ischemia/reperfusion（I/R）injury.Methods Twenty-one KM mice were randomly divided into sham group,intestinal ischemia group（with 45min ischemia and 24h reperfusion）,and curcumin treatment group.A mouse I/R model was established.The mice in intestinal ischemia and curcumin treatment groups were injected with 0.3ml PVP-K30 and 2.5mg/ml curcumin respectively,and repeated them after 6h.The mice were killed after 24h.Pathological changes in intestine and liver were observed with hematoxylin and eosin（HE）staining.Dynamic levels of alarmine transferase（ALT）,lactate dehydrogenase（LDH）,and nobelium（NO）in liver tissues were measured using biochemical methods.Levels of cytosolic phospholipase A2（cPLA2）,phosphorylation of cytosolic phospholipase A2（p-cPLA2）,cyclooxygenase-2（COX-2）,andβ-actin were measured by Western blot.Results The pathological changes in intestine and liver were more significant in curcumin treatment group than in intestinlischemia group（P〈0.01）according to the Chiu′intestinal tissue injury assessment criteria.The ALT level was significantly lower while the NO level was significantly higher in curcumin treatment group than in intestinal ischemia group（P〈0.05）.No significant difference was found in LDH level between the two groups（P〉0.05）.Western blot showed that the expression levels of p-cPLA2 and COX-2 in liver were higher in intestinal ischemia group than in curcumin treatment group（P〈0.01）,and lower in curcumin treatment group than in intestinal ischemia group（P〈0.01）.No significant difference was found in expression levels of cPLA2 and β-actin between the two groups.Conclusion Curcumin can significantly improve liver damage caused by intestinal I/R by increasing the anti-oxidative ability of liver and regulating the expression of certain inflammation cytokines.