小剂量乙酰半胱氨酸对慢性肝损伤大鼠的治疗作用

目的 研究小剂量乙酰半胱氨酸(NAC)对四氯化碳(CCl4)所致大鼠慢性肝损伤的治疗作用.方法 93只SD大鼠随机分成2组,正常对照组15只和模型组78只.自造模之日开始,模型组大鼠皮下注射25％CCl4橄榄油溶液1 mL/kg,正常组大鼠注射同剂量橄榄油溶液,每周3次,连续4周.4周末,模型组随机取3只进行病理切片检查,观察肝损伤严重程度.将造模成功的大鼠随机分成5组,每组15只,分别为小剂量NAC 45、90、180 mg/kg组、阳性对照组和模型组.阳性对照组给予还原型谷胱甘肽(GSH)54 mg/kg,正常对照组和模型组给予同容积灭菌生理盐水,腹腔注射每日1次,连续4周,末次给药后24 h,麻醉大鼠,腹主动脉取血,检测血清ALT、AST、白蛋白(ALB)、ALP和TBil,取肝脏称重,取部分检测肝组织中丙二醛(MDA)、羟脯氨酸(Hyp)、SH含量与超氧化物歧化酶(SOD)活力,剩余肝脏用10％福尔马林固定,切片观察肝脏组织病理变化.结果 各组间ALT、AST、ALP、ALB和TBil差异均有统计学意义(F=16.878、9.996、6.099、5.002、11.157,P＜0.01).模型组大鼠血清中ALT、AST、ALP和TBil分别为(112.00±19.05) U/L、(150.67±18.15) U/L、(272.75±34.26) U/L和(1.98±0.10) μmol/L,均高于对照组(t=26.912,P＜0.01;t=15.571,P＜0.01;t=8.238,P＜0.05;t=14.367,P＜0.01).各组间肝组织SOD、MDA、GSH和Hyp差异均有统计学意义(F=3.251,P＜0.05;F=3.232,P＜0.05;F=5.210,P＜0.01;F=41.131,P＜0.01).模型组肝脏MDA和Hyp分别为(0.99 ±0.22) nmol/mgprot和(504.02±84.51) μg/g,高于对照组(t=8.229和69.853,P＜0.01).小剂量NAC低、中剂量组GSH、Hyp和SOD均高于模型组,差异均有统计学意义(P均＜0.05).高剂量组GSH为(1.53±0.76) μmol/gprot,高于模型组;Hyp为(131.53±44.85) μg/g,低于模型组,差异均有统计学意义(t=6.023,P＜0.05;t=58.532,P＜0.01).HE染色结果表明所有NAC剂量组其肝脏病变程度均较模型组明显减轻.结论 小剂量NAC对CCl4诱导大鼠慢性肝损伤具有明显的治疗作用.

Therapeutic effect of low dose acetylcysteine on rats with chronic hepatic injury

Objective To investigate the effect of low dose acetylcysteine (NAC) on carbon tetrachloride (CCl4) induced chronic hepatic injury in rats.Methods A total of 93 SD rats were ranged into control group (n=1 5) and model group (n=78).Rats in model and control group were given 25％ CCl4 olive oil solution and olive oil 1 mL/kg respectively by subcutaneous injection,3 times a week continuously for 4 weeks.At the end of the fourth week,3 rats were randomly selected from the model group for pathological section,and observed the severity of liver damage.At the same time,75 rats with chronic hepatic injury were ranged into 5 groups with 15 rats in each groups with NAC 45,90,180 mg/kg,positive model group and model group.Rats in positive model group were given 54 mg/kg glutathione (GSH),and rats in control group and model group were given the same volume sterilized normal sodium,once a day by intraperitoneal injection for 4 weeks.The rats were narcotized and took blood from aorta abdominalis,hepatic function indices including ALT,AST,albumin (ALB),ALP and TBil in serum were detected 24 hours after the last administration,Livers were taken and weighted,and malonaldehyde (MDA),hydroxyproline (Hyp),GSH content and superoxide dismutase (SOD) activity in hepatic tissue were detected.The residual liver was fixed with 10％ formalin,and the histopathological changes were observed.Results The differences ofALT,AST,ALP,ALB and TBil in each group were statistically significant (F=16.878,9.996,6.099,5.002,11.157,P＜0.01).Compared with rats in control group,levels of ALT,AST,ALP and TBil in serum in model group,which were (112.00±19.05)U/L,(150.67±18.15)U/L,(272.75±34.26)U/L and (1.98±0.10)U/L respectively,were significantly higher (t=26.912,P＜0.01;t=15.571,P＜0.01;t=8.238,P＜0.05;t=14.367,P＜0.01).The differences of SOD,MDA,GSH and Hyp among each group had statistical significance (F=3.251,P＜0.05;F=3.232,P＜ 0.05;F=5.210,P＜0.01;F=41.131,P＜0.01).The liver MDA and Hyp in model group were (0.99±0.22)nmol/mgprot and (504.05±84.51)μg/g,which were higher than the control group (t=8.229 and 69.853,P＜0.01).GSH,Hyp and SOD in the small dose NAC group and middle dose group were higher than model group with significant differences (P all＜0.05).GSH in high dose group was (1.53±0.76)μmol/gprot which was higher than model group,while Hyp inmodel group in high dose group was (131.53±44.85) μg/g which was lower than model group (t=6.023,P＜0.05;t=58.532,P＜0.01).The HE staining results showed that all NAC groups could relieve the degree of chronic hepatic injury obviously.Conclusions Low dose NAC can prevent CC14 induced chronic hepatic injury in rats.