肝腹水灵口服液对四氯化碳诱导大鼠肝纤维化的抑制作用

肝纤维化是诸多慢性肝病向肝硬化发展的必经病理过程,目前尚无有效而理想的治疗药物,寻找安全有效的抗肝纤维化药物是治疗慢性肝病的当务之急.本研究应用CCl4造成大鼠实验性肝损伤肝纤维化模型,观察了肝腹水灵口服液对肝功能、HA、TNFα及肝脏的病理变化等的影响,以探讨临床抗肝纤维化治疗的新途径.

AIM:Vascular smooth muscle cell (SMC) proliferation and migration from the arterial wall media into the intima are believed to play a critical role in the pathogenesis of restenosis. Several studies have demonstrated that phosphothioate (PS) oligodeoxynucleotides targeted against genes involved in SMC proliferation inhibits in vitro SMC proliferation and migration. However, the therapeutic effect of antisense ODN on the individual who receives the treatment of delivery of the agent depends on the efficacy of this agent in great degree. We investigated the inhibition effect of a novel agent, insulin-antisense-c-myb-PS-ODN on SMC proliferation in vitro.　METHODS：The rat aortic artery SMCs were cultured in Dulbecco's modified Eagel's medium. The passage 8 to 13 were used as the experiment. Cell surface receptor binding assay was quantified through counting gamma particles emitted from 125　　　　I labeled insulin. SMC rapid proliferation was brought by stimulation of high concentration of fetal bovine serum (FBS). The novel agent of insulin conjugated to the antisense-c-myb-PS-ODN was obtained via incubation of both in condition of certain reagents, pH, temperature, and ion concentration. The characterization and purification of the agent was performed through HPLC. Inhibition of SMC proliferation was reflected by incorporation rate of trillium labeled thymidine deoxyribonucleotide.RESULTS：The binding efficacy of insulin to the receptor was remarkably increased in SMC cultured in supplement of 20% FBS. The inhibition effect of conjugator insulin-c-myb-antisense-PS-ODN was stronger than that of the simple c-myb-antisense-PS-ODN. The inhibition rate of conjugator and simple form on SMC proliferation were 48.34% and 29.54%, respectively. CONCLUSION：The binding efficacy and specificity of c-myb-antisense-PS-ODN to SMC may be enhanced by the insulin receptor mediation through the insulin-insulin receptor interaction. The insulin-receptor targeted method may be a potential and specific therapeutic pathway for restenosis.