The Mechanism Of Jiangtangsanhuang Tablet On The Diabetic Gardiomyopathy Left Ventricular Remodeling

The first part:literature researchDiabetic 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 researchObjective: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.