降糖三黄片干预糖尿病心肌病早期心室重构的作用机理研究
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摘要
第一部分文献研究
糖尿病心肌病是糖尿病的主要慢性并发症之一。糖尿病心肌病(diabetic cardiomyopathy,DC)指在糖尿病状态下,排除了高血压、冠心病及其他可以引起心脏异常的因素,导致一系列结构异常,并最终导致左心室肥大,舒张和＼或收缩功能减退——心室重构的病理改变。病变早期的心室重构与糖尿病患者高心力衰竭发病率和死亡率密切相关。目前,关于其发病机制还不清楚,涉及代谢紊乱、组织结构异常、局部病理生理改变等多个方面。现代医学认为多个信号转导通路参与了糖尿病心肌病的心室重构过程,通过西药干预这些通路中的环节能够在临床上起到一定的防治心室重构的作用。
中医古籍中无糖尿病心肌病的记载,根据本病的临床表现可归属于“消渴病心病”“心悸”、“怔忡”、“胸痹”、“厥心痛”等病范畴。“久病必虚”、“久病必瘀”,临床表现以心气虚、心阴虚为主,兼夹血瘀。治疗多采用益气健脾、养阴生津、活血化瘀、温阳利水等方法。心室重构不是一种独立的中医病证,它往往与一些疾病的部分症状和阶段性表现有关,涉及“心悸”、“怔忡”、“水肿”、“喘证”、“痰饮”、“心水”、“心痹”等范畴。基本病机为本虚标实,本虚以气虚、阳虚为主,标实以瘀血、水饮、痰湿居多,临床表现多为虚实夹杂。中药对糖尿病心肌病心室重构的调控作用主要体现在对其诱发因素的预防,以改善症状,减少并发症为主。通过对其上游病因如高糖、高脂、RAS激活等进行早期干预,抑制细胞因子的分泌和表达,减轻心肌损伤程度,来阻断心室重构的过程,从而改善心功能。
中医药治疗糖尿病心肌病具有整体调节的特色,其疗效显著,副作用少,而且远期疗效亦较稳定,具有比西药更大的优势。本学科早在上世纪80年代就开展了对2型糖尿病的中医防治研究,围绕气阴不足、瘀血阻络的病机,采用经方桃核承气汤为基础加味研制成降糖三黄片,在临床上治疗2型糖尿病取得显著疗效。进一步深入研究降糖三黄片对于包括糖尿病心脏病在内的糖尿病慢性并发症的疗效及作用机制对于其在临床的广泛应用具有深远的意义。
第二部分实验研究
目的：观察中药降糖三黄片对糖尿病心肌病大鼠早期心室重构的影响,并进一步从信号转导机制入手探讨该方对糖尿病心肌病的治疗作用及其作用机理。
方法：清洁级Wistar大鼠普通饲料适应性喂养1W后,改用高脂高热量饲料喂养一个月。造模前禁食12h,造模组按30mg/kg剂量腹腔内注射STZ,正常组腹腔内注射等量柠檬酸缓冲液。1W后,测定空腹血糖和空腹胰岛素,计算胰岛素敏感指数。连续两次空腹血糖≥11.1mmol/L,查尿糖++以上,胰岛素敏感指数降低,且有多饮、多尿、多食现象确认为2型糖尿病模型。2型糖尿病大鼠成模后,予高脂饲料连续喂养8W,即出现糖尿病大鼠的心肌损害(以电镜结果为证)。随机分为正常组与造模组(含模型组与治疗组)。糖尿病造模成功后造模组进一步分层,随机分为模型组、降糖三黄片干预组,卡托普利干预组。共49只大鼠完成实验,正常组10只,模型组13只,降糖三黄片干预组13只,卡托普利干预组13只(余5只或死亡或不符合条件)。降糖三黄片组药量按787.5mg/kg/d的剂量给予,卡托普利组药量按照4mg/kg/d的剂量给予,正常组及模型组灌服等量蒸馏水。①STZ注射后1周后大鼠禁食12h后空腹眼眶静脉窦采血,糖尿病大鼠造模成功后8周,处死前腹主动脉采血检测FBG、胆固醇和甘油三酯以及胰岛素。②糖尿病大鼠造模成功后8周采用超声心动图评价各组大鼠心脏的结构和功能,摘取心脏称重计算左室重量指数；③电镜观察各组心肌超微结构；④放免法检测各组心肌组织中AngⅡ含量；⑤免疫组化法检测心肌组织中ERK1／2的含量；⑥实时定量逆转录-聚合酶链反应检测心肌c-fos mRNA的表达。
结果：①模型组大鼠较正常组欠活泼,多精神萎靡；皮毛明显缺少光泽,色灰黄。造模后24h,模型组大鼠即出现尿量明显增加,其后摄食量及饮水量较正常组大鼠逐渐增加。正常组大鼠体重逐渐增加,模型组大鼠体重在造模后24h时无明显变化,48h时体重较造模前明显减少,72h至1周大鼠体重趋于稳定,1周后模型组大鼠体重与正常组大鼠有显著差异(P<0.01)；至8周实验结束时模型组和西药组体重明显低于正常组,有显著差异(P<0.01),而中药组体重明显高于西药组,两者相比具有显著性差异(P<0.01)。1周后造模各组的血糖、血脂升高、胰岛素敏感指数下降,同正常组相比具有显著性差异(P<0.05),8周后降糖三黄片组血糖、血脂水平明显下降,胰岛素敏感指数上升,同模型组和卡托普利组比较有显著性差异(P<0.05)；②超声心动图检查显示,在模型组,反映左室舒张功能的指标Em/Am显著降低,反映左室收缩功能的指标LVEF和Sm显著降低,同正常组相比具有显著性差异(P<0.05),上述结果提示本研究建立的动物模型符合2型糖尿病心肌病。在此基础上发现实验末模型组大鼠左室重量、左室重量指数均显著增加,同正常组相比具有显著性差异(P<0.05),说明在糖尿病心肌病基础上出现了心室的重构,为今后糖尿病心肌病心室重构的实验研究提供了良好的载体。中药降糖三黄片能够改善心功能各项指标,降低左室重量指数,其作用与西药卡托普利相似,两组比较无统计学差异(P<0.05)。③光镜显示模型组心肌细胞排列紊乱,细胞核大小不甚规则,细胞内可见肌纤维断裂、排列紊乱心肌细胞肥大、变性、灶性坏死,坏死区纤维化；肌间小动脉血管内膜及内膜下增生、纤维化及PAS阳性物质沉积,管腔变窄,毛细血管基底膜增厚及毛细血管瘤形成,心肌间质的明显纤维化；电镜显示模型组大鼠心肌细胞排列紊乱,肌原纤维呈灶性溶解,线粒体肿胀,外膜不完整,嵴减少与稀疏,胞核染色质凝聚,核膜不完整并呈节段性溶解消失。降糖三黄片能有效改善糖尿病心肌病大鼠的心肌超微结构,其效果与西药卡托普利相似；④模型组大鼠心肌AngⅡ水平明显高于正常组,两者具有显著性差异(P<0.05),而降糖三黄片组及卡托普利组心肌AngⅡ水平明显下降,且二者相比无显著性差异(P>0.05)。⑤模型组大鼠心肌细胞胞浆ERK1／2水平明显高于正常组,两者具有显著性差异(P<0.05),而降糖三黄片组及卡托普利组心肌的ERK1／2水平明显下降,且二者之间无显著性差异(P>0.05)。⑥模型组大鼠心肌细胞胞浆c-fos mRNA表达水平明显高于正常组,两者具有显著性差异(P<0.05),而降糖三黄片组及卡托普利组心肌的c-fos mRNA表达水平明显下降,二者之间无显著性差异(P>0.05)。
结论：①中药降糖三黄片不仅能从客观指标上降低糖尿病大鼠的血糖、血脂水平,改善胰岛素抵抗,还能够明显改善糖尿病大鼠“三多一少”的状态,体现了中医学整体观念的特点。②中药降糖三黄片能够改善糖尿病心肌病大鼠的心功能,降低左心室重量指数,改善心室重构,且其作用与西药卡托普利相似。③中药降糖三黄片改善糖尿病心肌病大鼠心室重构的作用机制可能与抑制AngⅡ／ERK/c-fos信号转导通路的活化有关。
The first part:literature research
Diabetic cardiomyopathy (DCM) is one of the chronic complications of T2DM. Although coronary artery disease is accelerated in the diabetic state,it has been recognized for a number of years that diabetes independently impairs myocardial performance by decreasing cardiac muscle function. Left ventricular hypertrophy, impaired ventricular contractive function and diastolic function is pathological features of ventricular remodeling, which is closely related to heart failure and mortality rate of T2DM. Pathogenesis of DCM is unclear., involving metabolic disorder, organization structure abnormal, local pathophysiologic changes etc. Modern medicine has proved that many signaling transduction pathway is involved in DCM ventricular remodeling, which is reversed through medication is the important measure for treating DCM.
There is no the name of DCM in ancient books of TCM. The clinical character of diabetic cardiomyopathy like many Chinese medicine's diseases,for example: "heart-throb", "palpitation", "chest Bi-syndrome", "precordial pain" etc. "long disease must be deficiency" " long disease must be stasis". Heart Qi deficiency, heart Yin deficiency and blood stasis is the most common clinical manifestation. Therapy of replenishing Qi to invigorate spleen, nourishing Yin and generating body fluid, activating blood to resolve stagnation, warming Yang and promoting diuresis is often used. Ventricular remodeling is not an independent disease and syndrome of TCM, it is related to the stage performance and symptom of some disease, involving "palpitation", "edema", "dyspnea", "phlegm and fluid", "heart obstruction". Its basic pathogenesis is deficiency origin and excess in superficiality. Qi and Yang deficiency, blood Stagnation, phlegm and fluid retention is common clinical menifestions, which is the excessive and the deficiency syndrome. Early intervention pathogenetic factors, such as high glucose and high fat, RAS activation, which may inhibit cytokine expression and alleviate myocardial injury, and improve symptom and reduce complications.
TCM had the whole regulation function on DCM, which is superior to western medicine with significant therapeutic effects, few side effects and stable long-term effects. My tutor professor Li and her teams carried out research on T2DM in the Twentieth Century. Development of Jiangtangsanhuang tablet with the classical prescription "Taohe Chengqi Decoction",which has notable curative effect on T2DM. Further study on DCM and other complications has profound significance.
The second part:experimental research
Objective:To observe the affection of Jiangtangsanhuang tablet on rats with diabetic cardiomyopathy (DCM) left ventricular remodeling, furthermore explore the role of glucose/AngⅡ/ERK/c-fos signal pathways in the development of DCM and the mechanism of Jiangtangsanhuang tablet.
Methods:Wistar rats were fed with high cholesterol diet throughout the study period, streptozocin (30mg/kg, i.p)was given at the 28th day, Jiangtangsanhuang tablet (787.5mg·kg-1·d-1,n=13)or Captopril (4mg·kg-1·d-1,n=13)was adiministerd at the 35th day to rats with fasting blood glucose≥11.1mmol/L per gavage for another 8 weeks. Control rats(n=10) were fed with regular chew. Control and pattern rats were treated with distilled water.①One and eight weeks after STZ rejection, fasting blood glucose and cholesterol and glycerin trimyristate and insulin levels were detected;②Eight weeks later,left ventricular function was determined by echocardiography, left ventricular weight index were calculated;③The ultrastructure of cardiomyopathy in diabetic rats observed by transmission electron microscope (TEM);④AngⅡcontent were detected through radioimmunoassay;⑤ERK1/2 content were detected with immunohistochemical method;⑥c-fos mRNA were detected by quantification real-time RT-PCR at the end of the study.
Rusults:①Compared with control rats, FBG and cholesterol and glycerin trimyristate was significantly increased and Insulin Sensitive Index (ISI)was significantly decreased in model group one weeks later after streptozocin (30mg/kg, i.p) injection (P<0.05). Jiangtangsanhuang tablet can significantly reduce FBG and cholesterol and glycerin trimyristate level, increase ISI level comparing with control and captopril rats (P<0.05).②Compared with model group, cardiac function was significantly improved in treated group with captopril and Jiangtangsanhuang tablet (P<0.05), but there was no difference between the latter two groups.③Compared with model group, the ultrastructure of cardiomyopathy was significantly improve in treated group with captopril and Jiangtangsanhuang tablet (P<0.05),but there was no difference between the latter two groups(P>0.05).④AngⅡcontent was significantly increase in model group (P<0.05), and the increase could be significantly attenuated by Jiangtangsanhuang tablet and captopril (P<0.05), but there was no difference between the latter two groups(P>0.05).⑤ERK content was significantly increase in model group (P<0.05), and the increase couble be significantly attenuated by Jiangtangsanhuang tablet and captopril (P<0.05). but there was no difference between the latter two groups(P>0.05).⑥The expression of c-fos mRNA was significantly increase in model group (P<0.05), and the increase couble be significantly attenuated by Jiangtangsanhuang tablet and captopril (P<0.05), but there was no difference between the latter two groups(P>0.05).
Conclusion:①Jiangtangsanhuang tablet can significantly reduce FBG and cholesterol and glycerin trimyristate level, ameliorate insulin resistance, moreover, it can significantly improve "threemoresandoneless" symptoms, which embody the concept of holism is basic characteristics of TCM.②Compared with model group, the cardiac function and left ventricular remodeling was significantly improve, the left ventricular weight index was significantly reduced in rats with DCM treated with Jiangtangsanhuang tablet, the overall curative effects was similar with captopril.③The pathway of glucose/AngⅡ/ERK/c-fos might play an important role in DCM. It may be one of the mechanism of Jiangtangsanhuang tablet to ameliorate DCM left ventricular remodeling.
糖尿病心肌病是糖尿病的主要慢性并发症之一。糖尿病心肌病(diabetic cardiomyopathy,DC)指在糖尿病状态下,排除了高血压、冠心病及其他可以引起心脏异常的因素,导致一系列结构异常,并最终导致左心室肥大,舒张和＼或收缩功能减退——心室重构的病理改变。病变早期的心室重构与糖尿病患者高心力衰竭发病率和死亡率密切相关。目前,关于其发病机制还不清楚,涉及代谢紊乱、组织结构异常、局部病理生理改变等多个方面。现代医学认为多个信号转导通路参与了糖尿病心肌病的心室重构过程,通过西药干预这些通路中的环节能够在临床上起到一定的防治心室重构的作用。
中医古籍中无糖尿病心肌病的记载,根据本病的临床表现可归属于“消渴病心病”“心悸”、“怔忡”、“胸痹”、“厥心痛”等病范畴。“久病必虚”、“久病必瘀”,临床表现以心气虚、心阴虚为主,兼夹血瘀。治疗多采用益气健脾、养阴生津、活血化瘀、温阳利水等方法。心室重构不是一种独立的中医病证,它往往与一些疾病的部分症状和阶段性表现有关,涉及“心悸”、“怔忡”、“水肿”、“喘证”、“痰饮”、“心水”、“心痹”等范畴。基本病机为本虚标实,本虚以气虚、阳虚为主,标实以瘀血、水饮、痰湿居多,临床表现多为虚实夹杂。中药对糖尿病心肌病心室重构的调控作用主要体现在对其诱发因素的预防,以改善症状,减少并发症为主。通过对其上游病因如高糖、高脂、RAS激活等进行早期干预,抑制细胞因子的分泌和表达,减轻心肌损伤程度,来阻断心室重构的过程,从而改善心功能。
中医药治疗糖尿病心肌病具有整体调节的特色,其疗效显著,副作用少,而且远期疗效亦较稳定,具有比西药更大的优势。本学科早在上世纪80年代就开展了对2型糖尿病的中医防治研究,围绕气阴不足、瘀血阻络的病机,采用经方桃核承气汤为基础加味研制成降糖三黄片,在临床上治疗2型糖尿病取得显著疗效。进一步深入研究降糖三黄片对于包括糖尿病心脏病在内的糖尿病慢性并发症的疗效及作用机制对于其在临床的广泛应用具有深远的意义。
第二部分实验研究
目的：观察中药降糖三黄片对糖尿病心肌病大鼠早期心室重构的影响,并进一步从信号转导机制入手探讨该方对糖尿病心肌病的治疗作用及其作用机理。
方法：清洁级Wistar大鼠普通饲料适应性喂养1W后,改用高脂高热量饲料喂养一个月。造模前禁食12h,造模组按30mg/kg剂量腹腔内注射STZ,正常组腹腔内注射等量柠檬酸缓冲液。1W后,测定空腹血糖和空腹胰岛素,计算胰岛素敏感指数。连续两次空腹血糖≥11.1mmol/L,查尿糖++以上,胰岛素敏感指数降低,且有多饮、多尿、多食现象确认为2型糖尿病模型。2型糖尿病大鼠成模后,予高脂饲料连续喂养8W,即出现糖尿病大鼠的心肌损害(以电镜结果为证)。随机分为正常组与造模组(含模型组与治疗组)。糖尿病造模成功后造模组进一步分层,随机分为模型组、降糖三黄片干预组,卡托普利干预组。共49只大鼠完成实验,正常组10只,模型组13只,降糖三黄片干预组13只,卡托普利干预组13只(余5只或死亡或不符合条件)。降糖三黄片组药量按787.5mg/kg/d的剂量给予,卡托普利组药量按照4mg/kg/d的剂量给予,正常组及模型组灌服等量蒸馏水。①STZ注射后1周后大鼠禁食12h后空腹眼眶静脉窦采血,糖尿病大鼠造模成功后8周,处死前腹主动脉采血检测FBG、胆固醇和甘油三酯以及胰岛素。②糖尿病大鼠造模成功后8周采用超声心动图评价各组大鼠心脏的结构和功能,摘取心脏称重计算左室重量指数；③电镜观察各组心肌超微结构；④放免法检测各组心肌组织中AngⅡ含量；⑤免疫组化法检测心肌组织中ERK1／2的含量；⑥实时定量逆转录-聚合酶链反应检测心肌c-fos mRNA的表达。
结果：①模型组大鼠较正常组欠活泼,多精神萎靡；皮毛明显缺少光泽,色灰黄。造模后24h,模型组大鼠即出现尿量明显增加,其后摄食量及饮水量较正常组大鼠逐渐增加。正常组大鼠体重逐渐增加,模型组大鼠体重在造模后24h时无明显变化,48h时体重较造模前明显减少,72h至1周大鼠体重趋于稳定,1周后模型组大鼠体重与正常组大鼠有显著差异(P<0.01)；至8周实验结束时模型组和西药组体重明显低于正常组,有显著差异(P<0.01),而中药组体重明显高于西药组,两者相比具有显著性差异(P<0.01)。1周后造模各组的血糖、血脂升高、胰岛素敏感指数下降,同正常组相比具有显著性差异(P<0.05),8周后降糖三黄片组血糖、血脂水平明显下降,胰岛素敏感指数上升,同模型组和卡托普利组比较有显著性差异(P<0.05)；②超声心动图检查显示,在模型组,反映左室舒张功能的指标Em/Am显著降低,反映左室收缩功能的指标LVEF和Sm显著降低,同正常组相比具有显著性差异(P<0.05),上述结果提示本研究建立的动物模型符合2型糖尿病心肌病。在此基础上发现实验末模型组大鼠左室重量、左室重量指数均显著增加,同正常组相比具有显著性差异(P<0.05),说明在糖尿病心肌病基础上出现了心室的重构,为今后糖尿病心肌病心室重构的实验研究提供了良好的载体。中药降糖三黄片能够改善心功能各项指标,降低左室重量指数,其作用与西药卡托普利相似,两组比较无统计学差异(P<0.05)。③光镜显示模型组心肌细胞排列紊乱,细胞核大小不甚规则,细胞内可见肌纤维断裂、排列紊乱心肌细胞肥大、变性、灶性坏死,坏死区纤维化；肌间小动脉血管内膜及内膜下增生、纤维化及PAS阳性物质沉积,管腔变窄,毛细血管基底膜增厚及毛细血管瘤形成,心肌间质的明显纤维化；电镜显示模型组大鼠心肌细胞排列紊乱,肌原纤维呈灶性溶解,线粒体肿胀,外膜不完整,嵴减少与稀疏,胞核染色质凝聚,核膜不完整并呈节段性溶解消失。降糖三黄片能有效改善糖尿病心肌病大鼠的心肌超微结构,其效果与西药卡托普利相似；④模型组大鼠心肌AngⅡ水平明显高于正常组,两者具有显著性差异(P<0.05),而降糖三黄片组及卡托普利组心肌AngⅡ水平明显下降,且二者相比无显著性差异(P>0.05)。⑤模型组大鼠心肌细胞胞浆ERK1／2水平明显高于正常组,两者具有显著性差异(P<0.05),而降糖三黄片组及卡托普利组心肌的ERK1／2水平明显下降,且二者之间无显著性差异(P>0.05)。⑥模型组大鼠心肌细胞胞浆c-fos mRNA表达水平明显高于正常组,两者具有显著性差异(P<0.05),而降糖三黄片组及卡托普利组心肌的c-fos mRNA表达水平明显下降,二者之间无显著性差异(P>0.05)。
结论：①中药降糖三黄片不仅能从客观指标上降低糖尿病大鼠的血糖、血脂水平,改善胰岛素抵抗,还能够明显改善糖尿病大鼠“三多一少”的状态,体现了中医学整体观念的特点。②中药降糖三黄片能够改善糖尿病心肌病大鼠的心功能,降低左心室重量指数,改善心室重构,且其作用与西药卡托普利相似。③中药降糖三黄片改善糖尿病心肌病大鼠心室重构的作用机制可能与抑制AngⅡ／ERK/c-fos信号转导通路的活化有关。
The first part:literature research
Diabetic cardiomyopathy (DCM) is one of the chronic complications of T2DM. Although coronary artery disease is accelerated in the diabetic state,it has been recognized for a number of years that diabetes independently impairs myocardial performance by decreasing cardiac muscle function. Left ventricular hypertrophy, impaired ventricular contractive function and diastolic function is pathological features of ventricular remodeling, which is closely related to heart failure and mortality rate of T2DM. Pathogenesis of DCM is unclear., involving metabolic disorder, organization structure abnormal, local pathophysiologic changes etc. Modern medicine has proved that many signaling transduction pathway is involved in DCM ventricular remodeling, which is reversed through medication is the important measure for treating DCM.
There is no the name of DCM in ancient books of TCM. The clinical character of diabetic cardiomyopathy like many Chinese medicine's diseases,for example: "heart-throb", "palpitation", "chest Bi-syndrome", "precordial pain" etc. "long disease must be deficiency" " long disease must be stasis". Heart Qi deficiency, heart Yin deficiency and blood stasis is the most common clinical manifestation. Therapy of replenishing Qi to invigorate spleen, nourishing Yin and generating body fluid, activating blood to resolve stagnation, warming Yang and promoting diuresis is often used. Ventricular remodeling is not an independent disease and syndrome of TCM, it is related to the stage performance and symptom of some disease, involving "palpitation", "edema", "dyspnea", "phlegm and fluid", "heart obstruction". Its basic pathogenesis is deficiency origin and excess in superficiality. Qi and Yang deficiency, blood Stagnation, phlegm and fluid retention is common clinical menifestions, which is the excessive and the deficiency syndrome. Early intervention pathogenetic factors, such as high glucose and high fat, RAS activation, which may inhibit cytokine expression and alleviate myocardial injury, and improve symptom and reduce complications.
TCM had the whole regulation function on DCM, which is superior to western medicine with significant therapeutic effects, few side effects and stable long-term effects. My tutor professor Li and her teams carried out research on T2DM in the Twentieth Century. Development of Jiangtangsanhuang tablet with the classical prescription "Taohe Chengqi Decoction",which has notable curative effect on T2DM. Further study on DCM and other complications has profound significance.
The second part:experimental research
Objective:To observe the affection of Jiangtangsanhuang tablet on rats with diabetic cardiomyopathy (DCM) left ventricular remodeling, furthermore explore the role of glucose/AngⅡ/ERK/c-fos signal pathways in the development of DCM and the mechanism of Jiangtangsanhuang tablet.
Methods:Wistar rats were fed with high cholesterol diet throughout the study period, streptozocin (30mg/kg, i.p)was given at the 28th day, Jiangtangsanhuang tablet (787.5mg·kg-1·d-1,n=13)or Captopril (4mg·kg-1·d-1,n=13)was adiministerd at the 35th day to rats with fasting blood glucose≥11.1mmol/L per gavage for another 8 weeks. Control rats(n=10) were fed with regular chew. Control and pattern rats were treated with distilled water.①One and eight weeks after STZ rejection, fasting blood glucose and cholesterol and glycerin trimyristate and insulin levels were detected;②Eight weeks later,left ventricular function was determined by echocardiography, left ventricular weight index were calculated;③The ultrastructure of cardiomyopathy in diabetic rats observed by transmission electron microscope (TEM);④AngⅡcontent were detected through radioimmunoassay;⑤ERK1/2 content were detected with immunohistochemical method;⑥c-fos mRNA were detected by quantification real-time RT-PCR at the end of the study.
Rusults:①Compared with control rats, FBG and cholesterol and glycerin trimyristate was significantly increased and Insulin Sensitive Index (ISI)was significantly decreased in model group one weeks later after streptozocin (30mg/kg, i.p) injection (P<0.05). Jiangtangsanhuang tablet can significantly reduce FBG and cholesterol and glycerin trimyristate level, increase ISI level comparing with control and captopril rats (P<0.05).②Compared with model group, cardiac function was significantly improved in treated group with captopril and Jiangtangsanhuang tablet (P<0.05), but there was no difference between the latter two groups.③Compared with model group, the ultrastructure of cardiomyopathy was significantly improve in treated group with captopril and Jiangtangsanhuang tablet (P<0.05),but there was no difference between the latter two groups(P>0.05).④AngⅡcontent was significantly increase in model group (P<0.05), and the increase could be significantly attenuated by Jiangtangsanhuang tablet and captopril (P<0.05), but there was no difference between the latter two groups(P>0.05).⑤ERK content was significantly increase in model group (P<0.05), and the increase couble be significantly attenuated by Jiangtangsanhuang tablet and captopril (P<0.05). but there was no difference between the latter two groups(P>0.05).⑥The expression of c-fos mRNA was significantly increase in model group (P<0.05), and the increase couble be significantly attenuated by Jiangtangsanhuang tablet and captopril (P<0.05), but there was no difference between the latter two groups(P>0.05).
Conclusion:①Jiangtangsanhuang tablet can significantly reduce FBG and cholesterol and glycerin trimyristate level, ameliorate insulin resistance, moreover, it can significantly improve "threemoresandoneless" symptoms, which embody the concept of holism is basic characteristics of TCM.②Compared with model group, the cardiac function and left ventricular remodeling was significantly improve, the left ventricular weight index was significantly reduced in rats with DCM treated with Jiangtangsanhuang tablet, the overall curative effects was similar with captopril.③The pathway of glucose/AngⅡ/ERK/c-fos might play an important role in DCM. It may be one of the mechanism of Jiangtangsanhuang tablet to ameliorate DCM left ventricular remodeling.
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