壳聚糖治疗大鼠非酒精性脂肪性肝病的初步实验研究

目的探索不同剂量壳聚糖治疗非酒精性脂肪性肝病的效果。方法60只大鼠随机分为空白对照组（10只）、脂肪肝模型组（20只）和3个不同剂量壳聚糖治疗组（各10只）。脂肪肝模型组和治疗组先用高脂饲料（含88％普通饲料＋10％猪油＋2％胆固醇）喂养12周。壳聚糖治疗组在13～20周每日经灌胃给予相对分子质量为127100壳聚糖溶液1次。三组的剂量分别为每公斤体质量0．094g、0．188g和0．375g。20周时处死动物,分别取肝组织切片观察脂肪变、炎症和纤维化情况,血清行生化指标检测。结果模型组动物均形成F4级脂肪变、G1～G2炎症和S1～S2纤维化。模型组动物ALT、AST、ALP、TC和LDL均较空白对照组显著升高。TG增高和HDL降低差异无统计学意义。与模型组相比,壳聚糖治疗各组大鼠肝脂肪变和炎症差异无统计学意义;但治疗组肝纤维化有明显好转。大剂量壳聚糖治疗组中60％大鼠肝纤维化减轻到S0期,无S2期。壳聚糖治疗组的生化指标也有一定程度的好转,但未恢复到空白对照组水平。结论大剂量壳聚糖（每日0．375g／kg）对改善大鼠肝组织的脂肪肝和纤维化有明显效果,对生化指标改善也有一定效果。

Experimental study of treatment of nonalcoholic fatty liver disease with chitisan in rats

Objective To investigate the effects of different doses of chitosan in the treatment of nonalcoholic fatty liver disease（NAFLD） in rats. Methods Sixty male rats were divided into normal controlled group （10 rats）, NAFLD model group （20 rats） and chitosan treatment groups with 3 different doses of chitosan （0. 094 g, 0. 188 g, 0. 375 g per kilogram of body weight per day）. The rats of NAFLD model group and chitasan treatment group were fed with high fat content diet （88% ordinary feed ＋ 10% lard oil ＋ 2% chlesterol） for 12 weeks. The chitosan treatment groups continued to receive high fat content diet and chitosan solution by means of a stomach catheter once a day. The rats were killed at the end of 20 weeks. The liver tissues were examined by histologic sections for steatosis, inflammation and fibrosis. The serum was analyzed for biochemical parameters. Results F4 steatosis, G1-G2 inflammation and S1-S2 fibrosis were developed in NAFLD model group. In comparison with normal controlled group, biochemical parameters including ALT, AST, ALP, TC and LDL were increased significantly in NAFLD group. In chitosan treatment groups, the degrees of steatosis and inflammation did not change significantly in comparison with the NAFLD model group, but the fibrosis was markedly improved in chitosan treated rats. In the group treated with high dose of chitosan, 60% rats were in S0 stage of fibrosis, with no S2 stage of fibrosis. Biochemical parameters of the animals in chitosan treatment group had some improvement, but did not return to levels of normal controlled group. Conclusion Improvement of liver tissue fibrosis was observed in rats treated with chitosan, especially in the high dose group （0. 375 g/kg per day）. The biochemical parameters, caused by high fat content diet, were somewhat improved after 8 weeks of chitosan treatment.