匹格列酮对酒精性肝病预防效果的实验研究

Prophylactic effect of pioglitazone to alcoholic hepatic diseases in rats

目的研究匹格列酮对大鼠酒精性肝病的预防作用。方法100只SD大鼠随机分为空白对照组(20只)、模型组(40只)、匹格列酮组(40只)。空白对照组给予正常饮食;酒精性肝病模型组给予从5%递增到22%及54%浓度的梯度酒精;匹格列酮组在给予5%递增到22%及54%浓度的梯度酒精的同时,给予匹格列酮(5mg·kg-1·d-1)。于5周及10周后检测血清ALT、AST水平,并分别处死每组一半大鼠,取肝脏切片HE染色,光镜观察大鼠肝脏病理学形态改变。结果模型组5、10周后,血清ALT、AST分别为(63.0±9.9)、(84.0±10.6)和(82.0±12.5)、(163.0±21·4)U/L,与空白对照组相比显著升高(P均<0.05);5周后,45%(9/20)大鼠发生肝脂肪性变性;10周后,90%(18/20)大鼠发生肝脂肪变性,50%(10/20)大鼠出现酒精性肝炎的病理变化。匹格列酮组5、10周后,血清ALT、AST分别为(48.0±8.6)、(64.0±7.9)和(62.0±13.6)、(83.0±16.1)U/L,与模型组相比有显著降低(P均<0·05),与空白对照组相比有升高(P均<0.05);5周后,30%(6/20)大鼠发生肝脂肪变性;10周后,70%(14/20)大鼠发生肝脂肪变性,30%(6/20)大鼠出现酒精性肝炎的病理变化。结论匹格列酮在一定程度上对大鼠实验性酒精性肝病具有预防作用。

Objective To study the prophylactic effect of pioglitazone to alcoholic hepatic diseases in rats. Methods A total of 100 SD rats were randomly divided into blank control group（20） ,model group（40） and pioglitazone group（40）. Blank control group were given normal diet;model group were given gradient （5 % -22% ）and 54% alcohol ;pioglitazone group were given pioglitazoue （5 mg· kg^- 1· d^- 1 ） every day when given gradient（5 % - 22% ）and 54% alcohol. The levels of ALT and AST in serum of rats were detected on 5 th and 10th week respectively and then half of rats in each group were killed on 5th and 10th wecks. Slices of liver were stained by HE and the changes of pathology were observed. Results In model group, the levels of ALT and AST were （ 63.0 ± 9. 9 ）, （ 84.0 ± 10. 6 ） U/L and （ 82. 0 ± 12. 5 ）, （ 163.0 ± 21.4） U/ L respectively on 5th and 10th week, and there was significant increase compared with blank control group（P 〈 0. 05 ）. The fatty degenerations were found after 5 weeks in 45 % （9/20） of the rats ; the fatty degenerations were found in 90% （ 18/20 ） of the rats, and the changes of alcoholic hepatitis were found in 50% （10/20） of the rats after 10 weeks in the model group. In pioglitazone group ,the levels of ATL and AST were （48. 0 ± 8.6）, （64. 0 ± 7.9 ）U/L and （62. 0 ± 13.6）, （83.0 ± 16. 1 ） U/L respectively on 5 th and 10th week, and there was significant dicrease compared with model group （ P 〈 0. 05 ） and significant increase compared with control group （ P 〈 0. 05 ）. 30% （6/20） of the rats were found fatty degeneration after 5 weeks; 70% （14/20） were found fatty degeneration and 30% （6/20） were found alcoholic hepatitis after 10 weeks. Conclusions Pioglitazone has a prophylactic effect to alcoholic hepatic diseases in certain degree.