紫草素对大鼠重症急性胰腺炎并发急性肺损伤的抑制作用

Inhibitory effect of shikonin against severe acute pancreatitis and associated acute lung injury in rats

目的:探讨紫草素对大鼠急性胰腺炎(SAP)并发急性肺损伤(ALI)的抑制作用。方法:将24只雄性SD大鼠随机均分为对照组、模型组和治疗组。模型组与治疗组大鼠采用逆行胰胆管注入4%牛磺胆酸钠溶液的方法诱导SAP,对照组行假手术。治疗组大鼠在模型制备前2 h给予紫草素(50 mg/kg)灌胃,其余两组大鼠则以相同方式给与同体积的溶剂。术后6 h处死各组动物收集血、胰腺与肺组织标本,观察胰腺与肺组织病理学变化,检测血清中TNF-α、IL-6水平,肺组织湿干比以及肺组织中PI3K、磷酸化PI3K(p-PI3K)、NF-κB的表达。结果:对照组大鼠胰腺与肺组织均未见异常,模型组与治疗组胰腺与肺组织出现明显的病理改变,但治疗组胰腺与肺组织的病变程度均明显小于模型组,各组间胰腺与肺组织病理评分均有统计学差异(均P <0.05)。与对照组比较,模型组与治疗组血清TNF-α与IL-6水平、肺组织湿干比、肺组织p-PI3K/PI3K与NF-κB表达量均明显升高(均P<0.05),但治疗组以上指标的变化程度均明显小于模型组(均P <0.05)。结论:紫草素对大鼠的SAP及其并发的ALI均有抑制作用,其机制可能与减少炎症因子的释放以及降低肺组织PI3K-Akt-NF-κB通路活化有关。

Objective:To investigate the inhibitory effect of shikonin on severe acute pancreatitis(SAP)and associated acute lung injury(ALI)in rats.Methods:Twenty-four male SD rats were equally randomized into the control group,model group and treatment group.Rats in both model group and treatment group underwent SAP induction by retrograde pancreaticobiliary duct injection of 4%sodium taurocholate,while those in control group underwent a sham operation.Rats in treatment group were administered with shikonin(50 mg/kg)by gavage 2 h before model creation,while rats in the other two groups received vehicle of the same volume by the same fashion.Six hours after operation,ratsin each group were sacrificed and the blood samples as well as the pancreatic and lung tissue specimens were collected.The pathological changes in pancreatic and lung tissues were observed,the lung wet/dry weight ratio,the serum levels of TNF-αIL-6,and the expression levels of PI3 K,phosphorylated PI3 K(p-PI3 K)and NF-κB in lung tissue were determined.Results:No abnormalities were observed in the pancreatic and lung tissues from control group,while evident pathological lesions were found in the pancreatic and lung tissues from either model group or treatment group,but the degrees of pathological changes in both pancreatic and lung tissues from treatment group were milder than those from model group.There were significant differences in the pathological scores for pancreatic and lung tissues among the groups(all P<0.05).The serum levels of TNF-αand IL-6,the lung wet/dry weight ratios,as well as the p-PI3 K/PI3 K and NF-κB expression levels in the lung tissues in both model group and treatment group were significantly increased compared with control group(all P<0.05),but the changing amplitudes of above variables in treatment group were smaller than those in model group(all P<0.05).Conclusion:Shikonin has inhibitory effect against both SAP and associated ALI in rats.The mechanism may be related to its reducing the release of inflammatory factors and suppressing the activation of PI3 K-Akt-NF-κB pathway in the lung tissue.