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目的 了解褪黑素(MT)对大鼠免疫性肝纤维化的影响并初步探讨其机制。方法 ①大鼠腹腔注射(ip)猪血清(自制)制造模型;②MT分早期(与造模同时)、晚期(造模开始8周后)给药,并均分为10μg·kg-1与1000μg·kg-1两个剂量组;③阳性对照药选用秋水仙碱(col);④处死大鼠后用放射免疫法检测血清透明质酸(HA)水平,并测定其肝组织羟脯氨酸(Hyp)含量及脾淋巴细胞功能等。结果 ①造模第8周,模型组大鼠血清唾液酸(SA),肝脏Hyp含量及肝纤维化程度明显升高,脂多糖(LPS)诱导的脾细胞增殖反应明显降低;而血清丙氨酸氨基转换酶(ALT)、天门冬氨酸氨基转换酶(AST)及总蛋白(TP)含量,刀豆素A(ConA)诱导的脾细胞增殖反应与正常对照组比较无显著性。第12周模型组血清ALT、SA、HA含量,腹腔巨噬细胞(PMΦ)产生的白细胞介素1(IL1)水平,肝脏Hyp含量及肝纤维化程度明显升高,ConA和LPS诱导的脾细胞增殖反应明显降低。而血清AST、TP含量与正常对照组比较无显著性。②MT早期给药,1000μg·kg-1可使肝纤维化大鼠升高的血清SA、肝脏Hyp含量及肝纤维化程度明显降低。MT10μg·kg-1与1000μg·kg-1均可恢复肝纤维化大鼠低下的LPS诱导的脾细胞增殖反应。③MT晚期给药,10μg·kg-1和1000μg·kg-1均可使肝纤维化大鼠升高的血清ALT、SA和HA水
Objective To investigate the effect of melatonin (MT) on immune hepatic fibrosis in rats and its mechanism. Methods ① The rat model was established by intraperitoneal injection of porcine serum (ip); ② The rats were administered with both early and late modeling (MMT) and later (beginning 8 weeks after modeling) and were equally divided into 10μg · kg-1 and 1000μg · Kg-1 two doses; ③ positive control drug selection colchicine (col); ④ rats were sacrificed by radioimmunoassay after the determination of serum hyaluronic acid (HA) levels, and measured the liver hydroxyproline Hyp) content and spleen lymphocyte function. Results ① At the 8th week, the levels of serum sialic acid (SA), liver Hyp and hepatic fibrosis in model group were significantly increased, and the proliferation of spleen cells induced by lipopolysaccharide (LPS) was significantly decreased. Serum alanine ALT, AST, TP and ConA induced splenocyte proliferation were not significantly different from those in normal control group. Serum levels of ALT, SA, and HA in the model group at the 12th week were significantly higher than those in the control group (P <0.05). The level of interleukin 1 (IL1) produced by peritoneal macrophages (PMΦ), liver Hyp content and hepatic fibrosis were significantly increased. Proliferative response was significantly reduced. Serum AST, TP content compared with the normal control group was not significant. ②MT early administration, 1000μg · kg-1 can make rats with hepatic fibrosis increased serum SA, liver Hyp content and liver fibrosis significantly reduced. Both MT 10μg · kg-1 and 1000μg · kg-1 could restore low LPS-induced splenocyte proliferative responses in rats with hepatic fibrosis. ③ Late administration of MT, 10μg · kg-1 and 1000μg · kg-1 can elevate serum ALT, SA and HA in rats with hepatic fibrosis