L-精氨酸对酒精性肝脂肪变大鼠肝组织NOS表达及氧应激的影响

Effects of L-arginine on expression of nitric oxide synthase and oxidative stress in rat liver tissues with alcoholic hepatic steatosis

目的:探讨L-精氨酸对酒精性肝脂肪变大鼠肝组织NOS表达及氧应激的影响. 方法:采用在饮水中加入酒精的方法建立酒精性肝脂肪变动物模型.32只SD大鼠随机分成4组,每组8只.A,B组分别喂饲400 mL/L乙醇至16,20 wk;C组喂饲乙醇同B 组,自17 wk起腹腔注射L-精氨酸;D组为正常对照组. B,D组自17 wk起腹腔注射等量的生理盐水.应用免疫组化和逆转录多聚酶链反应(RT-PCR)的方法检测肝组织中NOS的蛋白和mRNA表达,同时测定肝组织中NO,MDA, GSH,SOD含量,并观察肝组织病理变化. 结果:A,B组肝组织出现了不同程度脂肪变性,B组更为显著(t=76.5,P<0.05).与D组相比,A,B组肝组织中NO,MDA含量、iNOS表达明显增高(P<0.01);GSH, SOD含量、eNOS表达明显降低(P<0.05)与B组相比,C组肝组织脂肪变性被逆转或明显减轻(t=62.5,P<0.05),NO 含量无显著改变,MDA含量、iNOS表达明显降低(P<0.05); GSH,SOD含量及eNOS表达明显升高(P<0.05). 结论:L-精氨酸对酒精性肝脂肪变的治疗作用可能与iNOS 表达降低、eNOS表达升高以及氧应激减轻有关.

AIM: To study the effects of L-arginine on the expression of nitric oxide synthase and oxidative stress in rat liver tissues with alcoholic hepatic steatosis. METHODS: The rat alcoholic hepatic steatosis models were made with ethanol supplied in the drinking water.32 SD rats were randomly divided into four groups (n =8 in each group). Rats were fed with 400 mL/L ethanol for up to 16 (group A) or 20 (group B) weeks. Rats in group C were fed with ethanol as rats in group B and administered with L-arginine by intraperitoneal injection from the 17th week. Group D was the normal control. Rats in groups B and D were administered normal saline by intraperitoneal injection from the 17th week. The expression of protein and mRNA of NOS in the liver was detected with immunohistochemistry and reverse transcription polymerase chain reaction. Meanwhile, NO, MDA, GSH,SOD contents were measured and histopathological changes were observed in the liver tissues. RESULTS: In groups A and B, different degrees of steatosis could be seen. Steatosis was more significant in group B than in group A (t=76.5, P<0.05). Compared to group D, NO and MDA contents and the expression of iNOS were significantly increased (P<0.01).However,GSH and SOD contents and the expression of eNOS were significantly decreased (P<0.05) in groups A and B. In comparison to group B, steatosis in the liver was reversed or significantly lessened (t=62.5, P<0.05), NO contents were unchanged, MDA contents and the expression of iNOS were significantly decreased (P <0.05), GSH and SOD contents and the expression of eNOS were markedly increased in the group C(P<0.05). CONCLUSION: The therapeutic effects of L-arginine on alcoholic hepatic steatosis are probably involved in decreased iNOS expression, increased eNOS expression and alleviated oxidative stress.