目的通过检测M受体各亚型在心肌上的mRNA表达量,研究大明胶囊对高脂血症大鼠降血脂作用的分子机制。方法制备高脂血症大鼠模型,尾静脉取血测血清中的总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、游离脂肪酸(FFA)、丙二醛(MDA)、超氧化物歧化酶(SOD)等血脂指标;Trizol法提取心肌总RNA,利用逆转录聚合酶链反应(RT-PCR)测定M₂、M₃、M₄、M₅4种M受体亚型mRNA的表达,观察其在高脂、正常和给药3种条件下的差异。结果高脂血症时血清中的TC、TG、LDL、FFA及MDA水平升高(P<0.05),HDL与SOD降低(P<0.05),经大明胶囊治疗后TC、TG、LDL、FFA及MDA水平降低(P<0.05),HDL与SOD水平上调(P<0.05)至近正常水平;比较高脂模型组与正常组M受体各亚型mRNA表达,结果M₂、M₄、M₅受体亚型表达减弱,M₃受体亚型表达增强,差别有统计学意义(P<0.05)。给大明胶囊后与高脂模型组比较M3受体亚型mRNA表达增强,M₂受体亚型表达减弱,且具有显著差异(P<0.05),M₄、M₅受体亚型mRNA表达无显著差异(P>0.05)。结论高脂血症大鼠模型建立成功,大明胶囊具有降血脂作用,并且M3受体的水平上调是大明胶囊降血脂作用的分子机制之一。

Objective To seek the molecular mechanism of decreasing blood lipid effect of Daming Capsule on hyperlipemic rat via studying the mRNA expression of the subtypes of M receptor in the myocardium. Methods Hyperlipemic rat model was made firstly, the blood was obtained via vena caudalis, the indexes in the serum, such as TC, TG, LDL, HDL, FFA, MDA, and SOD, were measured, the myocardial total RNA was extracted by Trizol method, the difference of the four subtypes of M receptor M₂, M₃, M₄, and M₅ mRNA expression in three groups of hyperlipemia, normal, and drug administration was compared by RT-PCR. Results The concentrations of TC, TG, LDL, FFA, and MDA in serum increased (P0.05), while the levels of HDL and SOD decreased (P<0.05). After the treatment by Daming Capsule, the concentrations of the preceding four indexes cut down, while the concentratins of the post two ones went up to nearly normal level. The mRNA expressions of each subtype of M receptor between the hyperlipemia group and normal group were compared, the expression of M₂, M₄, and M₅ receptors decreased (P<0.05), while the expression of M₃ increased (P<0.05), there were significant statistical differences among them. The level of M₃ receptor increased (P<0.05), but M₂ receptor decreased (P<0.05) after giving Daming Capsule comparing with hyperlipemia group. Moreover, the differences have statistical significance. the expression of M₄ and M₅ receptor mRNA have no significance difference (P<0.05). Conclusion Hyperlipemic rat model is successfully established. Daming Capsule has the effect of lowering blood lipid. Furthermore, the increasing the expression of M₃ receptor is one of the mechanisms that Daming Capsule decreases the blood lipid.

重大基础研究前期专项(2004CCA06700)