大黄素预处理对幼龄大鼠肝内胆汁淤积的保护作用

Protective effect of emodin pretreatment in young rats with intrahepatic cholestasis

目的探讨大黄素对肝内胆汁淤积幼龄大鼠的保护作用。方法将120只Sprague Dawley(SD)大鼠随机分为对照组、模型组及大黄素高、中、低剂量组,每组24只,对照组和模型组采用羧甲基纤维素钠溶液灌胃,其余组以不同剂量大黄素溶液灌胃。实验第5天各组(对照组除外)采用α-萘异硫氰酸酯(ANIT,50 mg/kg)一次性灌胃建立肝内胆汁淤积模型。ANIT灌胃后24、48、72 h各组分别处死8只大鼠,比色法检测各组血清总胆红素(TBIL)、直接胆红素(DBIL),总胆汁酸(TBA)、碱性磷酸酶(ALP)、γ谷氨酰转移酶(GGT)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,采用苏木精-伊红染色于光镜下观察各组不同时间点肝脏形态学改变。结果 24、48、72 h模型组较对照组血清TBIL、DBIL、TBA、ALP、GGT、ALT、AST水平均显著升高(P<0.01)。模型组造模后48 h较24 h及72 h时血清TBIL、DBIL、TBA、ALT、AST水平均有不同程度升高(P<0.05)。24、48、72 h大黄素各剂量组较模型组TBIL、TBA水平有不同程度降低(P<0.05)。24、48、72 h大黄素高、低剂量组较中剂量组血清TBA水平明显升高(P<0.05)。模型组大鼠48 h病理改变最重;大黄素各剂量组各时间点肝脏病理较模型组减轻,其中大黄素中剂量组较大黄素高、低剂量组比较改善更明显。结论大黄素可以改善ANIT诱导幼龄大鼠肝内胆汁淤积,中剂量组效果最好。

Objective To investigate the protective effect of emodin in young rats with intrahepatic cholestasis. Methods A total of 120 young Sprague-Dawley rats were randomly divided into control, model, and high-, medium-, and low-dose emodin groups, with 24 rats in each group. The rats in the control and model groups were given sodium carboxymethyl cellulose solution by gavage, while the other groups were given different doses of emodin solution by gavage. On the 5th day of experiment, alpha-naphthylisothiocyanate（ANIT, 50 mg/kg） was applied by gavage to establish the model of intrahepatic cholestasis in all groups except the control group. At 24, 48, and 72 hours after gavage, 8 rats in each group were sacrificed. Colorimetry was used to measure the serum levels of total bilirubin（TBIL）, direct bilirubin（DBIL）, total bile acid（TBA）, alkaline phosphatase（ALP）, gamma glutamyl transpeptidase（GGT）, alanine aminotransferase（ALT）, and aspartate aminotransferase（AST） in each group, and hematoxylin-eosin staining was applied to observe the morphological changes of the liver under a light microscope at different time points. Results Compared with the control group, the model group had significantly increased serum levels of TBIL, DBIL, TBA, ALP, GGT, ALT, and AST at the 24-hour, 48-hour, and 72-hour time points（P〈0.01）. In the model group, the serum levels of TBIL, DBIL, TBA, ALT, and AST showed varying degrees of increase at 48 hours after establishment of model, compared with the values at 24 and 72 hours（P〈0.05）. At 24, 48, and 72 hours, the high-, medium-, and low-doseemodin groups had varying degrees of reductions in the serum levels of TBIL and TBA compared with the model group（P〈0.05）; the high- and low-dose emodin groups had significantly increased serum levels of TBA compared with the medium-dose emodin group（P〈0.05）. The model group had the most severe pathological changes at 48 hours. Compared with the model group, the high-, medium-, and low-dose emodin groups showed certain improvement in pathological changes of the liver at each time point, and the medium-dose emodin group had better improvement compared with the high- and low-dose emodin groups. Conclusions Emodin can effectively improve ANIT-induced intrahepatic cholestasis in young rats, and medium-dose emodin shows the best effect.