Screening Of Chinese Medicinal Herbs And Active Sites Against Restenosis After Percutaneous Tranluminal Angioplasty

Percutaneous transluminal coronary angioplasty (PTCA) has become the most common major method to treat coronary atherosclerotic heart disease. However, restenosis (RS) which occurs in 30% to 50% of patients within 3~6 months is an important limitation of clinical application of this method. The prevention and cure of restenosis has become the keen spot in the research of cardiology. So far, the pharmacology mechanism of restenosis is not clear, and no successful method has been found. Natural plants, which are the significant resource to find new drugs, might be helpful to become a feasible method to prevent and cure restenosis.The research progress of prevention and cure of restenosis by Chinese medicinal herbs and effective constituent is summarized in this paper. According to the pharmacology mechanism of restenosis and pharmacologic action of drugs, 8 Chinese medicinal herbs and Chinese drugs pharmaceutics, including Lignum Sappan, Lightyellow Sophora Root, Tripterygium Hypoglaucum Hutch, Safflower, Rhubarb, Puerarin, Elemene and Artesunate, have been chosen for screening, and their effect to restenosis has been investigated. In this research RS after percutaneous transluminal angioplasty (PTA) is used to model the clinical restenosis after PTCA. The purpose of this research is screening the Chinese medicinal herbs against RS after PTA by rat's carotid balloon injured model, and finding out the active sites or constituents through gradual separation and pharmacodynamic action tracing. The main contents of research and conclusions are as follows:â‘ Screening of Chinese medicinal herbs against RS after PTA: The restenosis model was established by injuring the male SD rats'right carotids with 2.0F balloon catheter. Rats were divided into three groups randomly: normal group, model group, medicine group. Medicine group rats were administered medicine immediately after operation. All decoctions were given by way of intragastric administration, while the Chinese materia medica preparations were administered by intraperitoneal injection. Fourteen days later,the treated arteries were cutted, sliced and HE stained. The preventive and therapeutic effect to experimental artery restenosis was investigated by the histopathologic changes of arteries.The result of research indicated that the rats'carotid restenosis model injured by balloon catheter, which was applied to screening of drugs against RS after PTA, was successfully established. Among these eight kinds of drugs, Lignum sappan, lightyellow sophora root and elemene had good effect to RS after PTA. They were able to reduce percent area stenosis (PAS) and neogenesis intima area (NIA) efficiently and enlarge the lumen area (LA). The effect of lightyellow sophora root was the best of all, and its percent area stenosis (PAS) (P<0.01) was 34.21%, comparing with model group, which decreased 51.72%. Therefore, lightyellow sophora root was valuable to separate the active sites or effective constituents further.â‘¡Effect against RS after PTA of extractions of lightyellow sophora root: The chemical constituents in lightyellow sophora root were extracted by methanol initially. Then according to the principle of similar dissolves, methanolic extract was seperated by different polarity dissolvent further. Different polar constituents were dissolved in four extractions, including aether, chloroform (CHCl3), acetic ether (Et Ac) and aqueous phase. Chloroform desiccated extract was named Extract I, and the aether and Et Ac desiccated extractions were conflated together, and the mixture was named Extract II. Extract I and Extract II were used to animal experiment. The result showed that Extract I could reduce PAS (P<0.01) and neogenesis intima area (NIA) (P<0.05) efficiently and enlarge the lumen area (LA) (P<0.05). It was found that CHCl3 extract was the active site which contained the effective constituent against RS.â‘¢Study of compositions in CHCl3 extract and effect of its main compersition against RS: Chemical compositions in CHCl3 extract were detected qualitatively by color reaction and thin-layer chromatography (TLC). Yellowish-brown precipitate was emerged after dropwising Potassium Heptaiodobismuthate test solution, while dropwising potassium mercuric iodide test solution, yellow-white precipitate was appeared. These phenomenons demonstrated that alkaloid was contained in CHCl3 extract. The result of acid-base titration qauntitative experiment showed that the content of alkaloid in this site was 81.2%. Banlangen, which was extracted from lightyellow sophora root, was experimentized by dose of 80mg/kg and 40mg/kg. The result manifested the effcet against RS of Banlangen was obviously. Dose of 80mg/kg could reduce intima thickness and neogenesis intima area (NIA) (P<0.01), enlarge lumen area (LA) (P<0.01), and decrease percent area restenosis (PAS) (P<0.01). Therefore, it was concluded that Banlangen was the effective constituent against RS after PTA.