谷氨酰胺对非酒精性脂肪肝炎大鼠肠黏膜屏障的保护作用

The Protective Effect of Glutamine on the Intestinal Mucosa Barrier Function in Non-alcoholic Steatohepatitis Rats

目的探讨谷氨酰胺对非酒精性脂肪肝炎肠黏膜屏障功能的保护作用。方法32只SD大鼠随机分为正常对照组8只,给予普通饮食喂养;高脂饮食组24只,给予高脂饲料喂养,于8周末从高脂饮食组随机抽取8只大鼠处死作为单纯性脂肪肝组,剩余大鼠随机分为谷氨酰胺组、NASH组,谷氨酰胺治疗组在8周末加用谷氨酰胺灌胃。12周末处死所有大鼠,测定大鼠门静脉血浆中内毒素、腹主动脉血浆中D-木糖以及肠粘液中sIgA的水平,测定小肠组织匀浆中SOD的活性和MDA的含量,并测定大鼠血清中TG、TC、ALT、AST,HE染色观察肝脏病理改变。结果12周模型组大鼠血清ALT、AST明显升高,肝脏病理表现为脂肪性肝炎,谷氨酰胺治疗组大鼠血清ALT、AST明显下降(P<0.05),肝组织炎症活动计分也明显下降(3.25±1.49vs.4.38±1.06,P<0.05),但仍显著高于8周单纯性脂肪肝组大鼠水平(3.25±1.49vs.2.00±0.76,P<0.05)。谷氨酰胺治疗组肝细胞脂肪变性程度无显著变化。谷氨酰胺治疗组大鼠门静脉血浆中内毒素、腹主动脉血浆中D-木糖、小肠组织匀浆中MDA含量与模型组相比明显降低(P<0.05),肠黏液中sIgA的水平和小肠组织匀浆中SOD与模型组相比明显升高(P<0.05)。结论谷氨酰胺可以降低高脂饮食诱发的非酒精性脂肪性肝炎大鼠血清中转氨酶水平和肝组织炎症损伤,降低门静脉血中内毒素水平,但不能完全阻止炎症的进展,提示肠黏膜屏障功能的改变是非酒精性脂肪性肝炎发病的重要机制之一。

Objective To explore the effect of glutamine on the intestinal mueosa barrier function in non-alcoholic steatohepatitis rats. Methods Thirty-two SD rats were divided into control group（ n = 8 ） and fat-rich diet group（ n = 24） randomly. Rats in control group were given normal diet,rats in fat-rich diet group were given fat-rich diet. At the end of the 8th week,8 rats from fat-rich diet group randomly were saerefied as simple fatty liver disease group, the rest were divided into model group and glutamine treatment group. Furthermore,rats in glutamine treatment group were given glutamine after 8 weeks. All rats were saerefied at the end of the 12th week. The level of endotoxin, D-xylose,TG,TC, ALT and AST,intestinal tissue SOD and MDA as well as intestinal mucus sIgA were measured. The pathology of liver was observed by HE stain. Results The rats＇ livers presented the pathology of steatohepatitis with higher serum levels of ALT and AST in the 12 weeks model group. The serum levels of ALT and AST of glutamine treatment group decreased significantly. The hepatic inflammation scores also decreased markedly （3.25±1.49 vs. 4. 38±1.06, P 〈0.05）,but were still higher （ 3. 25 ± l. 49 vs. 2.00±0.76, P 〈0.05） than those in 8 weeks＇ simple fatty liver disease group. The degree of hepatoeyte steatosis did not change in the glutamine treatment group. The serum level of endotoxin,D-xylose and the MDA contents in intestinal tissue of glutamine treatment group decreased significantly （ P 〈 0.05 ）. The level of slgA and the SOD activity in intestinal tissue increased significantly（ P 〈 0.05 ）. Conclusion Glutamine can decrease the level of aminotransferase and ameliorate hepatic inflammation in rats with steatohepatitis induced by fatrich diet,decrease the level of endotoxin, but can not prevent the development of steatohepatitis. It suggests the change of intestinal mucosa barrier function is one of important factors in the pathogenesis of NASH.