大明胶囊对高脂血症大鼠心肌间隙连接蛋白43表达水平的影响

目的：通过观察大明胶囊治疗前后的高脂血症大鼠心肌间隙连接蛋白43的表达,阐述大明胶囊降血脂作用的分子机制。方法：Wistar大鼠40只分组,建立实验性大鼠高脂血症模型,分别是正常组、高脂模型组、大明胶囊高、中、低(200,100,50 mg·kg^-1·d^-1)剂量组,每组8只。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(NEFA)等血脂指标；Trizol法提取心肌总RNA,利用RT-PCR技术和免疫组织化学方法结合激光共聚焦技术,测定间隙连接蛋白43在正常、高脂、给药3种情况下的差异。结果：高脂血症时血清中的TC,TG,LDL及NEFA含量升高(P<0.05),HDL含量降低(P<0.05),经大明胶囊治疗后TC,TG,LDL及NEFA含量降低(P<0.05),HDL含量上调(P<0.05)至接近正常水平；与正常组比较高脂组和给药组心电图无明显改变,心率无显著性差异；高脂组与正常组比较间隙连接蛋白43mRNA表达显著减弱(P<0.05),给药组与高脂组比较间隙连接蛋白43 mRNA表达显著增强(P<0.05)；免疫组织化学结果高脂组与正常组比较间隙连接蛋白43表达显著减弱(P<0.05),给药组与高脂组比较间隙连接蛋白43表达显著增强(P<0.05)。结论：大明胶囊具有降血脂作用,其降血脂的药效机制与间隙连接蛋白43的表达改变有一定联系。

Effect of Daming capsule on expression of connexin43 isoforms in hyperlipemic rat's cardiac muscle

OBJECTIVE: To find the molecular mechanism of decreasing blood fat effect of Darning capsule on hyperlipemic rat, we study the expression of connexin43 in the myocardium before and after using the capsule. METHOD: Forty Wistar rats were randomly divided into 5 group: control group, hyperlipemia model group, Daming capsule group of high dose, middle dose and low dose (200, 100, 50 mg kg(-1) d(-1)). Each group had 8 rats. Hyperlipemic rat model was made firstly, the blood was obtained via vena caudalis and the indexes of TC, TG, LDL, HDL and NEFA in the serum were measured. The myocardial total RNA was extracted by Trizol method. To compare the expression of connexin43 in the following groups: hyperlipemia, normal and drug, we used the technique of RT-PCR, immunostaining and microconfoul. RESULT: The concentrations of TC, TG, LDL and NEFA in hyperlipemic serum were increased (P <0. 05), while that of HDL was decreased (P <0. 05). After treating with Daming capsule, the concentration of the preceding four indexes were decreased and the concentrations of HDL was increased up to nearly normal level. No significant difference was found in the ECG of the three groups. As compared with the normal group, the mRNA expressions of connexin43 in hyperlipemia group was weakened (P <0.05), while that of the drug group was enhanced(P <0.05). The same result in immunostaining was observed. CONCLUSION: Hyperlipemic rat model was successfully established and Daming capsule has the effect of lowering blood lipid. Furthermore, the molecular mechanism of Darning capsule is related with the change of Cx43 closely.