解毒通络方对实验性糖尿病心肌病变大鼠保护作用的初步研究

目的通过观察解毒通络方对糖尿病心肌病变(DCM)大鼠心肌过氧化物酶增殖物激活受体γ(PPARγ)表达及心肌结构功能的影响,探讨解毒通络方治疗糖尿病心肌病变的可能机制。方法100只Wistar大鼠,随机分为正常对照组8只和造模组92只。造模组腹腔注射链脲佐菌素(STZ)55 mg/kg诱导糖尿病模型,糖尿病成模大鼠继续喂养12周则DCM模型成立,将DCM模型大鼠随机分为:解毒通络方组、清热解毒组、吡格列酮组、DCM模型组,分别灌胃给予解毒通络方10.4 g/kg,清热解毒药2.7 g/kg,吡格列酮2.7 mg/kg,DCM模型组和正常对照组给予等体积的蒸馏水,共给药6周。实验结束时检测各组随机血糖(RBG)、超敏C反应蛋白(hs-CRP)、血脂总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、心功能指标左心室压峰值(LVSP)、左室舒张末期压(LVEDP)、左室内压最大上升速率(+dp/dtmax)、左室内压最大下降速率(-dp/dtmax)、T值(t-dp/dt)]以及观察心肌形态学改变;采用免疫组织化学检测心肌中PPARγ的表达。结果与正常对照组比较,DCM模型组大鼠体重显著下降(P0.01),随机血糖、hs-CRP、TC、TG和LDL-C均显著升高(P0.01,P0.05),HDL-C显著降低(P0.05),心功能明显下降,LVSP、+dp/dtmax、-dp/dtmax明显下降,LVEDP、t-dp/dt明显升高(P0.05),心肌组织PPARγ表达显著下降(P0.01);与DCM模型组比较,解毒通络方组和清热解毒组大鼠随机血糖、hs-CRP、TC、TG和LDL-C均显著降低(P0.01,P0.05),HDL-C显著降低(P0.05),心功能明显改善,LVSP、+dp/dtmax、-dp/dtmax明显升高(P0.05),LVEDP、t-dp/dt明显下降(P0.05),心肌组织PPARγ表达明显增加(P0.01)。结论解毒通络方和清热解毒药能明显改善DCM大鼠糖代谢、脂质代谢、心功能和心脏组织结构,对糖尿病心肌病变有保护作用,其机制可能与上调心肌组织PPARγ抑制炎症有关。

Protective effects of Jiedu Tongluo Fang on rats with diabetic cardiomy-opathy

Objective To explore the possible mechanism of Jiedu Tongluo Fang(Toxin-removing collat-eral-unblocking Formula,JDTLF)in the treatment of diabetic cardiomyopathy by observing its effects on the expression of peroxisome proliferator activated receptor gamma(PPARγ)and cardiac function in rats with diabetic cardiomyopathy.Methods 100 Wistar rats were randomly divided into normal control group (n =8)and diabetic model group (n =92).Diabetic model was built by using intraperitoneal in-jection of streptozotocin (STZ,55 mg/kg).Diabetic cardiomyopathy(DCM)model was built by feeding those rats for another 12 consecutive weeks.DCM model rats were randomly divided into JDTLF group, Qingre JieduYao(heat-clearing toxin-removing medicinal,QRJDY)group,pioglitazone group,and DCM model group.Except the DCMmodel group and the normal control group,the other 3 groups were orally gavaged with 10.4 g/(kg·d)JDTLF,2.7 g/(kg·d)QRJDY,and 2.7 mg/(kg·d)pioglitazone re-spectively.DCMgroup and NC group received distilled water for 6 weeks.At the end of the experiment, random blood glucose (RBG),blood lipid(TC,TG,LDL-C,and HDL-C),high sensitive C reactive protein (hs-CRP),cardiac function(LVSP,LVEDP,+dp /dtmax ,-dp /dtmax and t-dp /dt)and morphologi-cal changes were evaluated.Expression of PPARγin myocardium was measured with immunohistochemis-try.Results Compared with the NC group,body weight in DCM group decreased significantly (P <0.01);Random blood glucose,hs-CRP,TC,TG and LDL-C increased significantly (P <0.01,P <0.05);HDL-C decreased significantly (P <0.05),and cardiac function decreased significantly;LVSP,+dp /dtmax ,-dp /dtmax decreased significantly;LVEDP and t-dp /dt increased significantly (P <0.05). There was a significant decrease in the expression of myocardial PPARγ;Compared with DCM model group,random blood glucose in JDTLF group and QRJDY group decreased significantly;Hs-CRP,TC, TG and LDL-C decreased significantly (P <0.01,P <0.05 ),HDL-C increased significantly (P <0.05);Cardiac function improved in JDTLF group and QRJDY group;LVSP,+dp /dtmax and -dp /dtmax increased significantly (P <0.05);LVEDP and t-dp /dt decreased significantly (P <0.05);Expression of myocardial PPARγpresented an increasing tendency (P <0.01).Conclusion Jeidu Tongluo Fang and Qingre Jiedu Yao can significantly improve the glucose and lipid metabolism,heart function and heart tissue structure,and have protective effect on diabetic cardiomyopathy.Its mechanism may be related to the up-regulation of PPARγ.