比较两种制剂工艺的参芪苏心颗粒对垂体后叶素致急性心肌缺血大鼠的作用研究

Comparative Study on the Effect of Shenqi Suxin Granules of Two Preparations on Pituitrin Induced Acute Myocardial Ischemia in Rats

目的 比较水提取和水提醇沉制剂工艺的参芪苏心颗粒对垂体后叶素致急性心肌缺血(AMI)模型大鼠的作用差异。方法 SD大鼠随机分为5组,即正常组(灌胃等体积纯净水)、模型组(灌胃等体积纯净水)、培哚普利组(0.36 mg/kg)、参芪水醇组(6.40 g/kg)、参芪水提组(6.40 g/kg),灌胃7 d。空白组舌下注射等体积0.9%氯化钠注射液,其余各组舌下注射垂体后叶素(0.75 IU/kg)造模。ELISA法测定全血肌钙蛋白T(c TnT)、6-酮前列腺素F1α(6-keto-PGF1α)、内皮素-1(ET-1);免疫竞争法测定肌酸激酶同工酶MB(CK-MB)、血栓素B2(TXB2);硝酸还原酶法检测一氧化氮(NO);比色法测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、总抗氧化能力(T-AOC)、丙二醛(MDA)、Ca2+-Mg2+-ATP酶和Na+-K+-ATP酶活性指标。结果 与模型组相比,培哚普利片组、参芪水醇组和参芪水提组具有显著抑制cTnT和CK-MB水平的作用(P <0.01)。培哚普利片组、参芪水醇组、参芪水提组的6-keto-PGF1α和TXB2水平均有降低(P <0.01);培哚普利片组、参芪水提组可显著纠正6-keto-PGF1α/TXB2平衡,参芪水醇组具有纠正6-keto-PGF1α/TXB2平衡的作用,差异具有统计学意义(P <0.01或P <0.05)。培哚普利片组,参芪水醇组和参芪水提组均具有显著抑制ET-1水平,升高NO水平的作用(P <0.01)。培哚普利片组、参芪水醇组、参芪水提组均可显著升高SOD、CAT、T-AOC水平(P <0.01),抑制MDA升高(P <0.01)。参芪水醇组Ca2+-Mg2+-ATP酶活性和Na+-K+-ATP酶活性升高,差异具有统计学意义(P <0.01或P <0.05)。结论 参芪苏心方可通过抑制氧化应激、保护血管内皮、限制钙超载和促进血管舒张等方面,减少垂体后叶素引起的心肌损伤,与水提取方法相比,水提醇沉法具有更好的药理作用。

Objective:To compare the effects of Shenqi Suxin Granules made by two pharmaceutical process,water extraction and water extraction and alcohol precipitation,on acute myocardial ischemia(AMI)induced by pituitrin(PIT)in rats. Methods:SD rats,SPF grade,half male and half female,were randomly divided into 5groups,namely the blank group(gavage with equal volume of purified water),model group(gavage with equal volume of purified water),perindopril group(perindopril tert-butylamine tablet,0.36 mg/kg body weight),Shenqi water extraction and alcohol precipitation group(SWAG)(6.40 g/kg body weight),Shenqi water extract group(SWG)(6.40 g/kg body weight),all received intragastric administration for 7 days. The blank group was injected with equal volume of normal saline under the tongue to establish the model,and the other groups were injected with pit(0.75 IU/kg)under the tongue. Cardiac troponin T(c TnT),6-keto-prostaglandin F1α(6-Keto-PGF1α)and endothelin-1(ET-1)were determined by ELISA. Creatine kinase isoenzyme MB(CK-MB)and thromboxane B2(TXB2)were determined by immune competition method. Nitric oxide(NO)was detected by nitrate reductase.Superoxide dismutase(SOD),catalase(CAT),total antioxidant capacity(T-AOC),malondialdehyde(MDA),Ca-Mg2 +-ATPase and Na+-K+-ATPase were determined by colorimetry. Results:The perindopril group,SWAG and SWG had significant inhibitory effects on cTnT and CK-MB levels compared with the model group(P < 0.01). The levels of 6-Keto-PGF1α and TXB2 in the perindopril group,SWAG and SWG were decreased(P<0.01). The perindopril group and SWG significantly corrected the balance of 6-Keto-PGF1α/TXB2,while SWG had the effect of correcting the balance of 6-Keto-PGF1α/TXB2,and the difference was statistically significant(P < 0.01 or P <0.05). Perindopril group,SWAG and SWG all had significant effects on inhibiting ET-1 level and increasing NO leve(lP < 0.01). The levels of SOD,CAT and T-AOC in peridopril group,SWAG and SWG were significantly increased(P < 0.01),and the increase of MDA was inhibited(P < 0.01). The activities of Ca-Mg-ATPase and Na+-K+-ATPase in SWAG were significantly increased(P < 0.01 or P < 0.05). Conclusion:Shenqi Suxin Granules can reduce pit induced myocardial injury by inhibiting oxidative stress,protecting vascular endothelium,limiting calcium overload and promoting vasodilation. Compared with water extraction method,water extraction and alcohol precipitation method has better pharmacological effect.