基于基因芯片技术探讨逆针及逆灸对高脂血症大鼠差异性调控的机制研究

Hyperlipidemia is one of the key causative factors of non-alcohol fatty acid disease, stroke, and coronary heart disease. Compared with western medicine therapy, which takes side effects and lifelong medication as its disadvantages, acupuncture and moxibustion therapy, as a kind of green therapy, was proved to have obvious curative effects on hyperlipidemia by lots of clinical studies. However, its mechanism remains to be elucidated. Despite the complexity of the pathogenesis of the disease, this is partially due to the multipath regulatory characteristics of acupuncture and moxibustion, which means that single factor, gene, protein, or even signal pathway are insufficient for the fully explanation of the therapy’s intervention mechanism. Preventive acupuncture and moxibustion, in the domain of preventive medicine, concerns disease prevention by triggering qi of meridians and collaterals by acupuncture and moxbustion therapy before the onset, or during the early stage of the disease. It is of comparatively high application value and broad research prospect. Our pilot studies have proved the benign intervention effects of preventive acupuncture and moxibustion on blood lipid of hyperlipidemia rats, with the effects differ in onset time and scope of action. On this basis, this study further aims at the construction of the molecular network of the regulation of hyperlipidemia by preventive acupuncture and moxibustion, and the screening of the key genes with help of gene chip technology, in order to analyze the molecular network mechanism of the difference lies between curative effects of preventive acupuncture and preventive moxibustion, and provide evidence for acupuncture and moxibustion therapy on hyperlipidemia.

高脂血症是引起非酒精性脂肪肝、中风、冠心病等疾病的重要危险因素。西药治疗存在副作用且往往需终身服药。大量临床研究证实，针灸作为一种绿色疗法，对高脂血症有较明确的治疗作用，然而具体的作用机制尚不十分明确。这与高脂血症发病机制的复杂性有关，且针灸对机体的调控存在多途径的特点，单一的因子、基因、蛋白甚至信号通路并不能较完整的描绘出针灸对其干预机制。“逆针灸” 属于预防医学，指在机体健康无病、疾病发生之前或疾病轻浅之时, 预先应用针灸方法激发经络之气以预防疾病，有较高的应用价值和研究前景。我们的前期研究证实，逆针和逆灸对高脂血症大鼠的血脂均存在良性干预作用，但两者在起效时间及调节范围存在差异。本研究拟在此基础上，进一步利用基因芯片技术，初步构建逆针灸调控高脂血症的分子网络，筛选出起主导作用的相关基因，分析逆针和逆灸疗效差异的分子网络机制，为高脂血症的针灸治疗提供依据。

当前疾病医学逐渐出现向健康医学转变的趋势， 医学关注的对象也将从“已病”的人.群逐渐向“未病”人群扩展， 医学干预的切入点将逐渐提前。“治未病”是中医预防医学思想的重要体现。高脂血症是引起非酒精性脂肪肝、中风、冠心病等疾病的重要危险因素，致残、致死率高，严重危害人类健康。长期服用他汀类药物是目前西医临床治疗高脂血症的首选方案，该方法可以预防动脉硬化以及降低心血管疾病的发病率和死亡率， 但同时会产生一系列副作用。因此，寻求一种有效且副作用小的防治方案是当前临床的迫切需要。大量现代研究也证实，针灸作为一种无副作用的绿色疗法，对高脂血症有较明确的治疗效应。本课题探讨的“逆针灸” 属于中医“治未病”的一种干预方法，是在机体健康无病或疾病轻浅之时, 预先应用针灸方法激发经络之气以预防疾病，有较高的应用价值和研究前景。本研究观察了 “逆针灸”对高脂饮食大鼠血脂的防治调节特点，并利用基因芯片技术探讨了逆针及逆灸的防治机制。主要结果表明：①逆针和逆灸对大鼠血浆TC、TG、HDL、Apoa-1有良性调节作用，逆针的调节作用更快速，逆灸主要体现了针灸调节的后效应。②逆针及逆灸后，肝细胞炎性浸润及脂肪病变程度显著减轻，肝细胞脂肪滴面积百分比显著降低。③逆针和逆灸引起了大量基因表达的升高或降低，随机PCR验证证实了基因检测的准确性④GO及pathway分析表明，逆针及逆灸对高脂血症大鼠的调节通路同时存在共性及特应性。因此，该项目主要研究了逆针及逆灸对大鼠高脂血症防治调节的特点，并在基因层面对这两种干预方式的调节机制进行了分析， 初步探讨构建了这两种调节方式的分子网络机制，为临床高脂血症的防治提供了一定思路，充实了针灸“治未病”理论的现代科学内涵。