淤胆型肝病致VitE缺乏与周围神经损害的动物实验研究

Vitamin E defficiency and peripheral nerve injury induced by cholestasis:an animal experimental study

目的探讨淤胆型肝病时血清VitE浓度与周围神经损伤的关系。方法2周龄Wistar幼鼠随机分为对照组、肝病组和VitE治疗组(n=10),建立改良α萘异硫氰酸酯(ANIT)淤胆型肝病模型。观察6周(至8周龄),检测血清VitE浓度、血清总胆红素(TB)、结合胆红素(DB)和丙氨酸氨基转移酶(ALT)含量;观察肝脏、坐骨神经组织病理学改变;采用生物医学图像分析系统分析肝组织病变面积。结果肝病组和治疗组血清DB、TB值较对照组增高倍数分别为62.4、30.0和21.1、10.1;肝病组肝组织病变面积明显大于治疗组(P<0.001);血清中VitE含量明显低于对照组(P=0.004)和治疗组(P=0.016);坐骨神经有明显原纤维轴索变性和髓鞘脱失等病理改变,异常半薄切片数明显高于治疗组(P=0.02)。结论体内VitE不足是导致淤胆型肝病周围神经受损的重要原因;补充VitE能有效减轻周围神经损害,同时可明显降低血清TB、DB浓度,有效抑制ANIT所致肝损伤和肝纤维化。

Objective To determine whether there is an association between low serum concentrations of vitamin E （VitE） and peripheral nerve injury, and to investigate the therapeutic effects of VitE supplementation on peripheral nerve and hepatic injury induced by cholestasis. Methods Thirty 2-day-old Wistar rats were randomly assigned into 3 groups： Untreated hepatopathy group, VitE-treated hepatopathy group and Normal control group （n = 10 each ）. Cholestatic hepatopathy was induced by gastric lavage with α-Naphthyl isothiocyanate （ANIT, 60 mg/kg, once every two days for 6 weeks） in rats. The VitE-treated group received additionally VitE by gastric lavage （70 IU/kg, once daily for 6 weeks）. Serum VitE concentration was measured by high-performance liquid chromatography. Serum concentrations of total bilirubin （TB）, direct bilirubin （DB） and alanine aminotransferase （ALT） were measured by automated biochemical analyzers. The histopathol gical changes of liver and sciatic nerves were observed under light and electronic microscopes. Average areas of liver lesions were measured by automated image analysis. Results In Untreated hepatopathy group the serum DB concentration increased by 62.4 times and the serum TB concentration increased by 30.0 times compared with those of the Normal control group. Serum concentrations of DB and TB in the VitE-treated group were much lower than those of Untreated hapatopathy group, although they were higher than those of the Normal control group. The extent of necrosis and fibrosis in the liver of the Untreated hepatopathy group was significantly larger than in the VitE-treated group. The Untreated hepatopathy group showed lower serum VitE concentrations than the Normal control group （ P = 0. 004）. VitE treatment significantly increased the serum VitE concentrations, to the same as Normal control group. Pathologic changes were observed in the sciatic nerves in the Untreated hepatopathy group, including axonal degeneration and demyelination. VitE treatment significantly reduced the extent of pathologic changes in the sciatic nerves. The Untreated hepatopathy group had significantly more nerve transections with severe lesions than the VitE-treated group. Conclusions VitE deficiency may be the dominant cause of peripheral nerve injury in chotestatic hepatopathy. VitE treatment can effectively reduce the extent of peripheral nerve injury, decrease serum concentrations of TB and DB, and reduce the extent of liver injury and fibrosis induced by cholestatic hapatopathy.