氢饱和生理盐水对重症急性胰腺炎肺损伤的作用及对NOX2/ROS/NF-κB通路的影响

Effect of hydrogen-rich saline on lung injury secondary to severe acute pancreatitis in rats and its association with NOX2/ROS/NF-κB pathway

目的:探讨氢饱和生理盐水(HRS)对大鼠重症急性胰腺炎(SAP)肺损伤的影响及其与NOX2/ROS/NF-κB通路的关系。方法:72只雄性Wistar大鼠随机分为假手术组、SAP模型组(SAP组)、SAP模型+HRS治疗组(HRS组);SAP模型以胆胰管逆行注射5%牛磺胆酸钠制备;术后5min,HRS组经尾静脉注射HRS(6mL/kg),假手术组与SAP组以等体积生理盐水代替;术后3、12、24h分批剖杀大鼠,胰腺和肺组织行病理学检查,以及血清胰酶水平、肺组织丙二醛(MDA)与超氧化物歧化酶(SOD)水平、肺组织NOX2、NF-κB及TNF-α表达水平检测。结果:与假手术组比较,SAP组和HRS组大鼠各时间点均出现明显的SAP与肺损伤表现,表现为胰腺、肺组织病理学评分增加,血清胰酶水平升高,肺组织MDA含量升高、SOD活性降低(均P<0.05),但除胰酶水平外(均P>0.05),HRS组各损伤指标均明显低于SAP组(均P<0.05);术后12h免疫组化结果显示,SAP组和HRS组大鼠肺组织中NOX2、NF-κB和TNF-α的表达均较假手术组升高(P<0.05),HRS组上述指标均较SAP组明显低于SAP组降低(均P<0.05)。结论:HRS有减轻SAP大鼠肺损伤的作用,机制可能与抑制NOX2/ROS/NF-κB通路活性有关。

Objective： To investigate the effect of hydrogen-rich saline（HRS） on lung injury secondary to severe acute pancreatitis（SAP） in rats and its association with NOX2/ROS/NF-κB pathway.Methods： Seventy-two male Wistar rats were equally randomized into sham operation group, SAP model group（SAP group） and SAP model plus HRS treatment group（HRS group）. SAP model was induced by retrogradeinfusion of 5% sodium taurocholate into the biliopancreatic duct. Five minutes after operation, rats in HRS group underwent tail vein injection of HRS（6 m L/kg）, while those in sham operation group and SAP group were given the same volume of normal saline instead. Rats were sacrificed in four batches with equal number of animals at 3, 12 and 24 h after operation. Then, in each group of rats, the pathological examinations of pancreatic and lung tissues were performed, the serum levels of pancreatic enzymes, the malondialdehyde（MDA） content and superoxide dismutase（SOD） activity, and the expressions of NOX2, NF-κB, and TNF-α in lung tissue were measured. Results： Compared with sham operation group, rats in either SAP group or HRS group exhibited manifestations of SAP and lung injury, as evidenced by significantly increased pathological scores of the pancreatic and lung tissues, elevated serum pancreatic enzyme levels and lung MDA content, and reduced lung SOD activity（all P〈0.05）; but all these injury parameters in HRS group, except the pancreatic enzyme levels（all P〉0.05）, were significantly lower than those in SAP group（all P〈0.05）. R esults of the immunohistochemical staining at 12 h after operation showed that the expression levels of NOX2, NF-κB and TNF-α in lung tissue were significantly increased in both SAP group and HRS group compared with sham operation group（all P〈0.05）, while all those in HRS group were significantly lower in HRS group versus SAP group（all P〈0.05）.Conclusion： HRS can alleviate SAP-induced lung injury in rats, and the mechanism may be associated with inhibition of the activation of NOX2/ROS/NF-κB pathway.