The Research Of The Effect And Mechanism Of Tianma Gouteng Decoction Reversing Hypertension Myocardial Fibrosis

Hypertension is a prevalent disease that hazards our people's health in our country. Myocardial fibrosis is not only the main cardiac pathological change that bringed by hypertension, but also one of the main reasons that attribute to many cardiovascular events. So the research of restraining and reversing myocardial fibrosis is very important. Part I Theory ResearchThese years it has been indicated by the researches of in-country and overseas that the pathogenesis of myocardial fibrosis is the result of the balance between the synthesis and the degradation of myocardial collagen being destroyed. Most of the researches reversing myocardial fibrosis awfully focus on the factors that accelerate the synthesis of myocardial collagen in excess. But it is found that the degradation abnormity of myocardial collagen shows the very important effect in causing myocardial fibrosis by recent researches. In clinical researches, many antihypertensive drugs have been confirmed to have effect of reversing myocardial fibrosis. But their functionary ways are single, the effect of reversing myocardial fibrosis is limited and all of them have respective side effects. Chinese Traditional treatment has many especial advantages to hypertension. Many effective and less-side effective prescriptions have been found, and Tianma Gouteng Decoction is one of them. In some researches, it has been confirmed that Tianma Gouteng Decoction is effective in decreasing blood pressure. And in our former researches, we found that Tianma Gouteng Decoction was effective in decreasing blood pressure, left ventricular weight (LVW), left ventricular weight index (LVI) and myocardial collagen content (Coll) of the renal hypertension rat (RHR). Also it could decrease intramyocardial Ⅰ and Ⅲ typecollagen content. It showed that Tianma Gouteng Decoction had good effect of reversing myocardial fibrosis. But that's still not enough all-sided to discuss the mechanism of Tianma Gouteng Decoction reversing myocardial fibrosis.At the part of experimental research, we select the model of SHR, and try to discuss the extensive mechanism of Tianma Gouteng Decoction reversing myocardial fibrosis from two sides of inhibiting the excessive synthesis of myocardial collagen and accelerating the degradation of myocardial collagen. At the part of clinical research, we select the especial crowd-the elderly hypertensives that tend to complicate myocardial fibrosis more easily as our observed object. Thereby, such can offer the reference for generalizing and applying Tianma Gouteng Decoction in clinic. Part Ⅱ Experimental ResearchObjective: To validate the effect that Tianma Gouteng Decoction decrease blood pressure and reverse myocardial fibrosis, and discuss the mechanism that Tianma Gouteng Decoction reverse myocardial fibrosis.Method: 24 male WKY rats of 8 weeks old were normal rats group; 72 male spontaneously hypertensive rats(SHR) of 8 weeks old were randomly divided to 3 groups: Tianma Gouteng Decoction group, captopril group and SHR group, 24 each group. The treatment started after the experimental animals were purchased 4 days. The rats of all the four groups would be executed at 6, 14, 24 weeks respectively, 8 rats per group at a time. Observational content include: systolic blood pressure(SBP), left ventricular weight(LVW), left ventricular weight index(LVI), myocardial collagen concentration(Coll), perivascular circumferential area(PVCA), collagen volume fraction(CVF); at the same time, We also observed the level of ALDO and Ang Ⅱ in circulation and cardiac muscle, the expression of intramyocardial TGF - β 1 and IGF - 1, the content of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinase-1(TIMP-1)in serum.Results:1.Tianma Gouteng Decoction can evidently decrease the level of SBP, LVW, PVCA and Coll, P<0.01 comparing with SHR group at corresponding time; At early period of the curative intervention(after 6 weeks), Tianma Gouteng Decoction can not decrease the level of LVI and CVF(T6 vs S6, P>0.05), with the medicamentous intervention getting along, Tianma Gouteng Decoction can also decrease LVI and CVF obviously (P<0.05 or p<0.01). 2. First, except that there were no distinct difference between Tianma Gouteng Decoction group and SHR group about the level of Ang Ⅱ in cardiac muscle after 6 weeks(T6 vs S6, P=0.068), the level of AngⅡ and ALDO in circulation and cardiac muscle of the Tianma Gouteng Decoction group at other times was lower than the SHR group (P<0.01). Captopril had certain effect on AngⅡin circulation and cardiac muscle and ALDO in circulation, but had no effect on ALDO in cardiac muscle(K6 vs S6; K14 vs S14; K24 vs S24, all P>0.05). To the effect of decreasing the level of ALDO in cardiac muscle, Tianma Gouteng Decoction was better than captopril. Secondly, Tianma Gouteng Decoction can obviously inhibit the expression of intramyocardial IGF - 1 at different time(T6 vs S6;T14 vs S14;T24 vs S24, all P<0.01). At early period of the curative intervention(after 6 weeks), though Tianma Gouteng Decoction can inhibit the expression of intramyocardial TGF -β1, there were no distinct difference between Tianma Gouteng Decoction group and SHR group in statistic (T6 vs S6, P>0.05). With the medicamentous intervention getting along, Tianma Gouteng Decoction can also inhibit the expression of intramyocardial TGF - β1 evidently(T14 vs S14, P<0.05; T24 vs S24, P<0.01). Finally, Tianma Gouteng Decoction can accelerate the degradation of myocardial collagen: it can not only increase the level of MMP1 in serum, but also decrease the level of TIMP1 in serum. Captopril can only decrease the level of TIMP1 in serum, and have no effect on MMP1. At the anaphase of the curative intervention (after 24 weeks), the effect that Tianma Gouteng Decoction decrease the level of TIMP1 in serum was better than captopril (P<0.05).Conclusion: Tianma Gouteng Decoction has the steady and reliable effect of decreasing blood pressure and reversing myocardial fibrosis, the mechanism may be relevant to have influence on some factors hereinafter: (1)Decrease the level of AngⅡ and ALDO in circulation and cardiac muscle; (2)Inhibit the expression of intramyocardial TGF-β1 and IGF - 1; (3)Accelerate the degradation of myocardial collagen--increase thelevel of MMPl in serum, and decrease the level of TIMPl in serum. Comparing with captopril, the ways through which Tianma Gouteng Decoction reverse myocardial fibrosis are more diversiform, and Tianma Gouteng Decoction can reverse myocardial fibrosis much earlier. Part Ⅲ Clinical ResearchObjective: To observe clinical curative effect that Tianma Gouteng Decoction reserve myocardial fibrosis of the eldly hypertensives.Method: 60 patients that were diagnosed as elderly hypertension and hyperactivity'of...