丁苯酞对脓毒症大鼠肠系膜动脉内皮的保护作用

Protective effect of N-butylphthalide on the endothelium of mesenteric arteries in sepsis rat

目的:探讨丁苯酞(NBP)对脓毒症大鼠肠系膜动脉内皮的作用及其可能机制。方法:将40只SD大鼠均分为假手术(SHAM)组、脓毒症(CLP)组、丁苯酞低剂量干预(CLP+NBP-L)组、丁苯酞高剂量干预(CLP+NBP-H)组。观察大鼠术后24 h在体心功能及肠腔变化;HE染色观察肠系膜动脉的形态改变;酶联免疫吸附法和硝酸还原法检测大鼠血清中IL-6、TNF-α水平和肠系膜动脉匀浆中eNOS活性及NO含量;微血管张力测定系统检测各组肠系膜动脉张力变化。结果:与CLP组相比,CLP+NBP-L组和CLP+NBP-H组大鼠心功能改善(P<0.05),肠系膜动脉损伤减轻(P<0.05);血清中IL-6、TNF-α水平降低(P<0.05),肠系膜动脉eNOS活性及NO含量升高(P<0.05);微血管对ACh介导的舒张效应改善(P<0.05);经L-NAME、NS-2028分别孵育30 min后,肠系膜动脉对ACh介导的舒张功能减弱(P<0.001)。结论:NBP可改善脓毒症大鼠肠系膜动脉的舒张效应,其机制可能是通过调节NO-sGC-cGMP通路实现对内皮的保护作用。

Objective:To investigate the effect of N-butylphthalide on the endothelium of mesenteric arteries endothelium and the potential mechanism in rats with sepsis.Methods:Forty SD rats were equally randomized to sham operation(SHAM)group,sepsis(CLP)group,low-dose N-butylphthalide intervention(CLP+NBP-L)group,and N-butylphthalide high-dose intervention(CLP+NBP-H)group.The changes of intestinal lumen and cardiac function were observed in vivo 24 hour after operation.HE staining was used to observe the morphological changes of mesenteric microvascular tissues.Eenzyme-linked immunosorbent assay and nitric acid reduction method were used to measure the levels of IL-6 and TNF-αin rat serum as well as eNOS and NO levels in the homogenate of the rat mesenteric artery endothelia.Then the changes of the arterial tension was measured in each group of rats using microvascular tension measurement system.Results:Compared with the CLP group,the cardiac function of the CLP+NBP-L group and the CLP+NBP-H group was improved(P<0.05),and the mesenteric artery injury was alleviated(P<0.05).The levels of IL-6 and TNF-αin serum were decreased(P<0.05),and the activity of eNOS and NO content in mesenteric arteries was increased(P<0.05).The mesenteric artery improved the diastolic function mediated by ACh(P<0.001).After incubation with L-NAME and NS-2028 for 30 min,the ACh-mediated relaxation function of mesenteric artery was attenuated(P<0.001).Conclusion:N-butylphthalide can improve the diastolic effect of mesenteric arteries in septic rats,and its mechanism may be achieved by regulating the NO-sGC-cGMP pathway to protect endothelial function.