4-苯基丁酸对高脂饮食诱导大鼠非酒精性脂肪肝病的治疗作用

Therapeutic effect of 4-phenylbutyric acid on non-alcoholic fatty liver disease induced by high-fat diet in rats

目的:研究内质网应激(ERS)抑制剂4-苯基丁酸(4-PBA)对高脂饮食所致非酒精性脂肪肝病(NAFLD)大鼠的保护作用。方法:SD大鼠随机分为正常组、模型组、4-PBA组,除正常组外,其余大鼠给予高脂饮食8周复制NAFLD模型,采取4-PBA(350 mg/kg)进行灌胃,连续干预4周。计算大鼠体重变化,肝、肾、脾指数;测定血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、白蛋白(ALB)、球蛋白(GLB)、总蛋白(TP)、白/球比(A/G);测定肝脏中超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量;饱和油红O染色观察大鼠肝脏脂滴沉积;免疫组织化学法检测肝脏葡萄糖调节蛋白78(GRP78)表达水平。结果:与模型组比较,4-PBA组大鼠体重增加量、肝指数明显降低(P<0.05);血清中ALT、AST、GLB、TP、TC、TG、LDLC水平显著下降,HDL-C、A/G显著上升(P<0.05);肝脏中SOD、GSH、GSH-Px活性显著升高,MDA含量显著降低(P<0.05);油红O染色证实,肝细胞脂滴沉积面积显著减少(P<0.05);免疫组化表明,肝脏中GRP78表达水平显著降低(P<0.05)。结论:4-PBA对高脂饮食诱导NAFLD大鼠有一定的治疗作用,可能与改善氧化应激、调节脂质代谢紊乱及减轻ERS有关。

Objective:To study the protective effect of endoplasmic reticulum stress(ERS)inhibitor 4-phenylbutyric acid(4-PBA)on rats with non-alcoholic fatty liver disease(NAFLD)induced by high-fat diet.Methods:SD rats were randomly divided into normal group,model group,and 4-PBA group.Except for the normal group,the rats in other groups were given a high-fat diet for 8 weeks to construct the NAFLD model.4-PBA(350 mg/kg)was intragastrically administered for 4 weeks.The changes in body weight,and the index of liver,kidney,and spleen of rats were calculated.Serum alanine aminotransferase(ALT),aspartate transaminase(AST),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),albumin(ALB),globulin(GLB),total protein(TP),and albumin globulin ratio(A/G)were determined.Activity of superoxide dismutase(SOD),glutathione(GSH)and glutathione peroxidase(GSH-Px)as well as malondialdehyde(MDA)content in liver tissues were measured.Saturated oil red O staining was used to observe liver lipid deposition.The expression level of liver glucose regulatory protein 78(GRP78)was detected immunohistochemically.Results:Compared with the model group,in the 4-PBA group,the weight gain and liver index were significantly reduced(P<0.05);serum levels of ALT,AST,GLB,TP,TC,TG,LDL-C were significantly reduced,while the HDL-C and A/G were increased significantly(P<0.05);SOD,GSH,GSH-Px activity in liver were increased significantly,the MDA content was decreased significantly(P<0.05);oil red O staining confirmed that the area of liver cell lipid droplet deposition was decreased significantly(P<0.05);immunohistochemistry showed that the expression level of GRP78 in liver tissue was significantly reduced(P<0.05).Conclusion:4-PBA has a certain therapeutic effect on high-fat diet-induced NAFLD in rats,which may be related to improving oxidative stress,regulating lipid metabolism disorders and reducing ERS.