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目的研究小异源二聚体伴侣受体(small heterodimer partner,SHP)在急性淤胆型肝炎大鼠模型中的表达及大黄素的干预作用。方法 40只Sprague-Dawley(SD)大鼠随机分为4组:正常对照组,模型组,大黄素组,熊去氧胆酸(UDCA)组,每组10只。除正常对照组外,其余3组给予α-异硫氰酸萘酯(alphanaphthylisothiocyanate,ANIT)50 mg·kg~(-1)一次灌胃,建立大鼠急性淤胆型肝炎动物模型,并给予相应的药物干预,造模后48 h留取标本,以实时荧光定量PCR法及Western blot法分别检测肝组织中SHPm RNA表达及蛋白表达的变化;全自动生化分析仪检测血清总胆红素(total bilirubin,TB)、直接胆红素(direct bilirubin,DB)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、胆汁酸(total bile acid,TBA)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)、γ-谷氨酰转移酶(gamma glutamine transferase,GGT)的水平;肝组织切片、HE染色后显微镜下观察肝组织病理学改变。结果模型组肝组织中SHP m RNA及蛋白表达水平分别为0.559±0.194、0.313±0.087,均低于正常对照组(P<0.05),大黄素组肝组织中SHP m RNA及蛋白表达水平分别为0.892±0.390、0.706±0.193,均高于模型组(P<0.05);大黄素组血清TB、DB、ALT、TBA、AST、ALP均明显低于模型组(P<0.05),且大黄素组TB、DB、ALT、TBA、AST、ALP明显低于熊去氧胆酸组(P<0.05);大黄素组肝组织病理改变较模型组明显减轻,熊去氧胆酸组肝组织病理改变亦较模型组明显减轻,但程度重于大黄素组。结论大黄素可升高ANIT诱导的大鼠急性淤胆型肝炎肝组织中SHP m RNA及蛋白表达水平。大黄素可降低血清中TB、DB、ALT、TBA、AST、ALP水平及减轻肝组织病理学损害,疗效优于熊去氧胆酸,其作用机制与促进SHP表达有关。
Objective To study the expression of small heterodimer partner (SHP) in rat model of acute cholestatic hepatitis and the effect of emodin on it. Methods Forty Sprague-Dawley (SD) rats were randomly divided into 4 groups: normal control group, model group, emodin group and ursodeoxycholic acid (UDCA) group, 10 rats in each group. Except for the normal control group, the other three groups were given an intraperitoneal injection of 50 mg · kg -1 alphanaphthylisothiocyanate (ANIT) once a day to establish an animal model of acute cholestatic hepatitis in rats, The changes of SHPm RNA expression and protein expression in liver tissue were detected by real-time fluorescence quantitative PCR and Western blot respectively. The level of total bilirubin (total bilirubin, bilirubin, TB), direct bilirubin (DB), alanine aminotransferase (ALT), total bile acid (TBA), aspartate aminotransferase AST, alkaline phosphatase (ALP) and gamma-glutamine transferase (GGT). Liver sections were stained with HE for histopathological changes under the microscope. Results The expression of SHP m RNA and protein in liver tissue of model group were 0.559 ± 0.194 and 0.313 ± 0.087, respectively, which were lower than those of normal control group (P <0.05). The expression of SHP mRNA and protein in liver tissues of emodin group were 0.892 ± 0.390 and 0.706 ± 0.193, respectively, which were significantly higher than those in the model group (P <0.05). The levels of serum TB, DB, ALT, TBA, AST and ALP in the emodin group were significantly lower than those in the model group The levels of TB, DB, ALT, TBA, AST and ALP were significantly lower than those of ursodeoxycholic acid group (P <0.05). The pathological changes of liver tissue in emodin group were significantly reduced compared with model group, and the pathological changes of liver tissue in ursodeoxycholic acid group Compared with the model group was significantly reduced, but the degree is heavier than the emodin group. Conclusion Emodin can increase SHP m RNA and protein expression in the liver of rats with acute cholestatic hepatitis induced by ANIT. Emodin can reduce serum TB, DB, ALT, TBA, AST, ALP levels and reduce the pathological damage of liver tissue, the effect is superior to ursodeoxycholic acid, and its mechanism of action and to promote the expression of SHP.