| Theoretical ResearchHypertension, which directly threatens quality of life, is a major contributor to cardiovascular and cerebrovascular events. Over the past two decades, domestic and foreign scholars have agreed upon various standards in the treatment of hypertension, and considerable progress has been made in the field of antihypertensive drugs. Oral antihypertensive drugs represent a milestone in hypertension therapy. However, the blood pressure (BP) standard for patients with hypertension is far from satisfactory. The study of Chinese herbal formulas for treating hypertension has received much research attention. These studies seek to integrate traditional and Western medicine in China. Currently, Chinese herbal formulas are known to have an outstanding advantage with regard to bodily regulation. Research shows that Chinese herbal medicine (CHM) has multi-protected mechanisms such as smoothly controlling the blood pressure, reducing blood pressure variability, protecting target organs, reversing left ventricular remodeling, regulating renin-angiotensin-aldosterone system, reversing risk factors of hypertension, regulating metabolism of glucose and lipid, enhancing the insulin sensitivity, regulating vasoactive substances, improving endothelial function, inhibiting vascular smooth muscle cell proliferation, blocking calcium channels, improving life quality and clinical symptoms, and reversing uncontrollable factors of blood pressure. However, the effect of CHM on the primary endpoints is still unclear. The benefits of CHM for hypertension need to be confirmed in the future with randomized controlled trials (RCTs) of more persuasive primary endpoints and high-quality SRs.According to TCM theory, hypertension belongs to the category of vertigo. Therefore, TCM principles, which have been used to treat vertigo in clinical practice for centuries, have been applied to the treatment of hypertension by physicians in China. Consequently, it is widely accepted that hypertension should be treated based on the theory of liver-wind until now. However, due to the different understandings between vertigo and hypertension, it can’t be neglected that some new problems have arisen in treating hypertension. Previous treatment experience can’t solve these problems perfectly. Both specific differences between them and new understandings about the etiology, pathogenesis, diagnosis and treatment of hypertension are needed to be explored.It is worth noting that, the natural process of hypertension is changed directly because of constantly optimizing and widely using antihypertensive drugs, which results in the change of evolution law in traditional Chinese medicine pathology correspondingly. It is found out that kidney deficiency is the key pathology of hypertension nowadays. It is highly related to the following4reasons:physiological kidney deficiency due to the aged, pathological kidney deficiency due to chronic disease, the adverse effects of antihypertensive drugs, and the therapeutic function of antihypertensive drugs. Consequently, tonifying the kidney is an important therapeutic strategy for the treatment of hypertension.Bu shen jiang ya decoction (BSJYD) is a clinical experience prescription based on the therapeutic principle of tonifying kidney. Early literature researches and clinical studies have shown that BSJYD could contribute to lowering blood pressure and clinical symptoms in hypertensive patients with kidney deficiency syndrome. Therefore, aiming the two main objectives in the treatment of hypertension including stabilizing blood pressure and protecting target organs, this experimental study was designed to investigate the effect BSJYD on blood pressure and ventricular hypertrophy and its potential mechanisms.Experimental StudyObjective:To investigate the effect of BSJYD on blood pressure, heart rate, and ventricular hypertrophy in SHR, and the effect of BSJYD on microRNA-1that regulating ERK signaling pathway in LVH with SHR.Method:60male SHRs of12weeks old were randomly and equally divided into5groups:the untreated control group (SHR-C), BSJYD high dose group (SHR-Bh), BSJYD middle dose group (SHR-Bm), BSJYD low dose group (SHR-B1), and the positive control group (SHR-Ca), and they were treated respectively with distilled water, high dose BSJYD, middle dose BSJYD, low dose BSJYD, and captoprilby dissolving in equalvolume ofwater administrated via gavage for8weeks. Besides,12age matched Wistar-Kyoto (WKY) rats treated with distilled water were allocated in a normal control group. Blood pressure and heart rate were measured every2weeks. Rats were managed at22weeks. Myocardialpathology and left ventricular mass index (LVMI) were observed, and their mRNAexpressions of BDNF, Ras, ERK1/2, and c-fox were determined by Real-tmie PCR. the expressions of BDNF, Ras, ERK1/2, and c-fox were also determined by western blot (WB). miRNA-1was also measured by qRT-PCR.Results:(1) blood pressure:as compared with SHR-C, blood pressure in SHR-Bh, SHR-Bm, SHR-B1, and SHR-Ca were significantly lowered (P<0.05). As compared with SHR-Ca, SHR-Bm and SHR-B1were significantly elevated (P<0.05), while there is no significantly difference in SHR-Bh (P=0.257). Among them, blood pressure was decreased most significantly in SHR-Ca and SHR-Bh.(2) heart rate:as compared with SHR-C, heart rate in SHR-Bh were significantly lowered (P<0.01), while heart rate in SHR-Bm, SHR-B1, and SHR-Ca were not significantly lowered. As compared with SHR-Ca, SHR-Bh were significantly lowered (P<0.05), while there is no significantly difference in the other groups (P>0.05).(3) LVMI:as compared with WKY, LVMI in SHR-C, SHR-Ca, SHR-Bh SHR-Bm, and SHR-B1were significantly elevated (P<0.01). As compared with SHR-C, LVMI in WKY, SHR-Ca, and SHR-Bh were significantly lowered (P<0.05). As compared with SHR-Ca, LVMI in WKY was significantly lowered (P<0.01), while LVMI in SHR-C was significantly elevated (P<0.05).(4) BDNF, Ras, ERK1/2及c-fox mRNA:①In the mRNA expression of BDNF, as compared with WKY, BDNF in SHR-C, SHR-Ca, SHR-Bh SHR-Bm, and SHR-B1were significantly elevated (P<0.01). As compared with SHR-C, BDNF in WKY, SHR-Ca, SHR-Bh, and SHR-Bm were significantly lowered (P<0.01), while there is no differencr in SHR-B1(P>0.05). As compared with SHR-Ca, BDNF in WKY, SHR-C, SHR-Bh, SHR-Bm, and SHR-B1were significantly elevated (P<0.05).②In the mRNA expression of Ras, as compared with WKY, Ras in SHR-C, SHR-Bh SHR-Bm, and SHR-B1were significantly elevated (P<0.05), while there is no difference in SHR-Ca (P>0.05). As compared with SHR-C, Ras in WKY, SHR-Ca, SHR-Bh, and SHR-Bm were significantly lowered (P<0.01), while there is no differencr in SHR-B1(P>0.05). As compared with SHR-Ca, Ras in SHR-C and SHR-B1were significantly elevated (P<0.01), while there were no difference in WKY, SHR-Bh, and SHR-Bm.③In the mRNA expression of ERK1/2, as compared with WKY, ERK1/2in SHR-C, SHR-Bh SHR-Bm, and SHR-B1were significantly elevated (P<0.01), while there is no difference in SHR-Ca (P>0.05). As compared with SHR-C, ERK1/2in WKY, SHR-Ca, SHR-Bh, and SHR-Bm were significantly lowered (P<0.01), while there is no differencr in SHR-Bl (P>0.05). As compared with SHR-Ca, ERK1/2in SHR-C and SHR-Bl were significantly elevated(P<0.01), while there were no difference in WKY, SHR-Bh, and SHR-Bm (P>0.05).④In the mRNA expression of c-fox, as compared with WKY, c-fox in SHR-C, SHR-Ca, SHR-Bh SHR-Bm, and SHR-B1were significantly elevated (P<0.01). As compared with SHR-C, c-fox in WKY, SHR-Ca, SHR-Bh, SHR-Bm, and SHR-Bl were significantly lowered (P<0.01). As compared with SHR-Ca, c-fox in WKY, SHR-C, SHR-Bh, SHR-Bm, and SHR-Bl were significantly elevated (P<0.01).(5) mirRNA-1:as compared with WKY, mirRNA-1in SHR-C, SHR-Bh SHR-Bm, and SHR-Bl were significantly lowered (P<0.05), while there is no difference in SHR-Ca (P>0.05). As compared with SHR-C, mirRNA-1in WKY, SHR-Ca, SHR-Bh, SHR-Bm, and SHR-B1were significantly elevated (P<0.01). As compared with SHR-Ca, mirRNA-1in SHR-C, SHR-Bm, and SHR-B1were significantly lowered (P<0.05), while there were no difference in WKY and SHR-BhConclusion:(1) BSJYD could control blood pressure and reduce heart rate in SHR.(2) BSJYD could reverse LVH to a certain extent.(3) Hypertensive ventricular hypertrophy maybe caused by down-regulating microRNA-1to promote the overexpression of ERK signaling pathway and its key targets.(4) Mechanism of BSJYD reversing LVH maybe related to up-regulating microRNA-1to inhibite the expression of ERK signaling pathway and its key targets.(5) A dose-dependent effection was shown between SHR-Bh, SHR-Bm, and SHR-Bl. As compared with SHR-Bm and SHR-B1, SHR-Bh has shown better effect on reducing blood pressure and heart rate, reversing LVH, up-regulating microRNA-1, and inhibiting the expression of ERK signaling pathway. |
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