PFD对二甲基亚硝胺诱导的大鼠肝纤维化治疗疗效和CTGF表达的影响

目的观察不同剂量PFD对二甲基亚硝胺（Dimethylnitrosamine DMN）诱导大鼠肝纤维化的治疗作用和CTGF表达的影响,初步探讨其可能的作用机制。方法健康雄性Wistar大鼠105只随机分为正常组21只,给予生理盐水10 mg/kg体重腹腔内注射,每周前三天连续给药,1次/日,连续注射3周;造模组84只,给予1%DMN溶液10 mg/kg体重腹腔注射,每周前三天连续给药,1次/日,连续注射3周。两周末将造模组随机分为4组,每组21只,分别是：模型组、IFN-α治疗组、PFD 120 mg、PFD 240 mg治疗组。各组大鼠均于造模第3周第一天给予药物治疗,每周七天,1次/日,治疗共4周。各组给药剂量及方法如下：正常组、模型组予以0.5%CMCNa 6 m L/kg灌胃;PFD不同剂量组予以相应剂量PFD灌胃;IFN-α组予以IFN-α10万单位/只,皮下注射。治疗四周后处死所有大鼠,留取肝组织行Masson染色,免疫组织化学法测Ⅰ型胶原,CTGF表达。结果 （1）Masson染色SSS半定量评分,模型组与正常组比较显著升高（P〈0.05）。IFN-α组、PFD组SSS半定量评分较模型组显著降低（P〈0.05）。免疫组化法检测肝组织Ⅰ型胶原的表达,模型组与正常组比较显著升高（P〈0.05）,PFD组与模型组比较显著降低（P〈0.05）,IFN-α组与模型组比较无统计学差异（P〉0.05）,（2）免疫组化法检测肝组织CTGF的表达,模型组与正常组比较显著升高（P〈0.05）。PFD 120 mg、PFD 240 mg各组与模型组比较显著降低（P〈0.05）。结论 （1）PFD具有治疗DMN诱导的大鼠肝纤维化的作用,与α-IFN无明显差别。（2）PFD抗DMN诱导大鼠肝纤维化的作用机制可能与下调CTGF的表达,抑制促纤维化因子有关。

Effects of PFD on Dimethylnitrosamine - induced Hepatic Fibrosis and the Expression of CTGF in the Rats

Objective The aim of this study was to observe the effect of different doses of PFD in the treatment of fi- brosis experimentally induced in rats by chronic administration of dimethylnitrosamine（DMN） and to explore its possible mechanism. Methods Male Wistar rats （ n = 105 ） were randomly subdivided into normal group without modeling （ n = 21 ） , The rest 84 rats after 2 weeks of modeling were randomized into 4 groups ： model group （ n = 21 ） , PFD120mg group （ n = 21 ） , PFD240mg group （ n = 21 ） , IFN - α group （ n = 21 ）. The normal group received intraperitoneal injection of 10 mg/kg saline per rat every Monday, Tuesday and Wednesday for 3 weeks; while the model group, PFD treatment groups and IFN - αtreatment group received intraperitoneal injection of 10mg/kg DMN solution per rat. All groups received drug intervention once everyday, beginning from the Monday of 3rd week and lasting for four weeks. The detailed scheme was as follows： the normal group and model group were fed by gavage with 0. 5% CMC - Na 6ml/kg; the PFD groups of different doses were fed by gavage with the corresponding dose of PFD ; the IFN - αgroup received intraperito- neal injection of IFN - α 106 Unit. At the end of the 6th week, all the rats were killed. Meanwhile, we took liver in the same position of left liver to processe masson staining, immuno - histochemical staining of collagen I, CTGF. Results （ 1 ） The results of semi - quantity determination of masson staining in model group obviously rise, compared to normal group which has statistical meanings （P 〈 0.05 ）. The results in PFD group , IFN -α group decrease about 32% -52% and has statistical meanings （ P 〈 0. 05 ） compared with model group. The expression of collagen I in model group has sta- tistical meanings （ P 〈 0. 05 ） compared to normal group. The expression of collagen I in PFD group has statistical mean- ings （P 〈0.05） compared with model group. （2）The expression of CTGF in PFD 120 mg group,PFD240mg g