| Literature and theoretical research Theoretical researchBlood pressure (BP) response to changes in salt intake, namely salt-sensitivity, is present in approximately half of the hypertensive. Limiting salt intake could contribute to reduce the blood pressure in salt-sensitivity hypertension. The pathogenesis of salt sensitivity hypertension is related to genetic gene, neural mechanism and endocrine mechanism etc. Salt-sensitive hypertension has clinical manifestations that the kidneys and the heart damage occurred earlier with high blood pressure. Currently, the rapidly increasing incidence of hypertensive renal damage has become one of the most important reasons of End Stage Renal Disease. At this stage, domestic and foreign scholars have agreed upon various standards that blocking the development progress of hypertensive renal damage by lowering BP. However, control rate are still low and effective treatment of hypertension is limited by poor compliance and significant adverse reaction of antihypertensive drugs. Therefore, some patients have turned to Chinese medicine (CM), hoping that such treatments might improve the efficiency.TCM syndrome types of hypertensive renal damage are relatively complex without clearly record in ancient books. To simplify TCM syndrome differentiation and enable researchers not familiar with Chinese medicine to master the laws of hypertension syndrome differentiation, this paper retrospectively studied the literature for2434patients with hypertensive renal damage, published from1994to2014. This study is beneficial to deepening the understanding of hypertension and providing a basis and reference for clinical treatment using TCM syndrome differentiation. The most syndrome factors of hypertensive renal damage patients were Yin deficiency, yang hyperactivity, qi deficiency, blood stasis, and turbid phlegm. Syndrome targets were mainly in kidney and related with liver, collateral and spleen.TCM is a holistic system of healthcare developed by the Chinese and has been practiced for thousands of years. Effective treatment of hypertensive renal damage is limited by poor compliance and significant adverse reaction of antihypertensive drugs. Therefore, some patients have turned to Chinese medicine (CM), hoping that such treatments might improve the efficiency. However the core values of TCM never deviated from it. This study was intended to evaluate the efficacy and safety of TCM for hypertensive renal damage. A total of62studies (involving5890patients) were included. The methodological quality of the included trials was evaluated as generally low. Meta-analysis showed that CM combined with western medication, was more effective in lowering blood pressure (BP), blood urea nitrogen (BUN), serum creatinine (Cr), microalbuminuria (mALB) and β2-microglobulin (β2-MG) compared with western medication. Meta-analysis showed there are significant beneficial effect on BP, BUN, Cr, mAlb in CM using alone compare to the western medication. Only23trials reported adverse events without details, and the safety of CM is still uncertain.There is some but weak evidence about the effectiveness of TCM in treating patients with hypertensive renal damage.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, improving the level of serum biochemical indexes 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 renal damage in Dahl salt-sensitive rats (DS) and its potential mechanisms.Experimental StudyObjective:To investigate the effect of BSJYD on blood pressure, renal function, renal fibrosis and renal pathology in DS, and the effect of BSJYD on regulating TGF β/Smads signaling pathway in hypertensive renal damage with DS.Materials and Methods:48male DS of Five-week-old were randomly divided into low salt group and high salt group. Low salt group (LS) fed with0.4%salt diet, high salt group fed with8%high-salt diet. After three weeks of high salt rats, DS rats with8%high-salt diet were randomly and equally divided into three groups:high-salt group (HS), western medicine group (valsartan capsules, WM) and the CM group (BSJYD).8weeks of continuous administration. Blood pressure was measured once week. After8weeks rats were managed. Rat femoral artery blood serum was separated to determine BUN and Scr, UA levels, and observed morphological changes in the removal of right kidney, Routine HE staining, Masson staining were made after paraffin. The mRNA expressions of TGF β1, Smad2, Smad3, smad7and CTGF were determined by Real-time PCR, and protein expressions of TGF β1, p-Smad2/3, Smad7and CTGF were determined by Western blot.Result:(1) Blood pressure:blood pressure (BP) is no significant difference in each group with high salt diet (P>0.05), and higher than the low-salt group (P<0.01) before administration. After8weeks, as compared with the HS respectively, blood pressure in WM and BSJYD were significantly lowered (P<0.01). As compared with WM, BSJYD was no significantly elevated (P=0.70).(2) Renal function:①In the measurement of urea nitrogen (BUN), as compared with the HS, WM and BSYJD were significantly lowered (P<0.05); As compared with WM, BSJYD was no significantly elevated (P=0.41).②In the measurement of serum creatinine (Scr), as compared with the HS, WM and BSYJD were significantly lowered (P<0.05); As compared with WM, BSJYD was no significantly elevated (P=0.83).③In the measurement of uric acid (UA), as compared with the HS, WM and BSYJD were significantly lowered (P<0.05); As compared with WM, BSJYD was significantly elevated (P<0.05).(3) Renal pathology:No clearly Pathology change was seen in LS group. Degeneration and vacuolation of tubular epithelium occurred and interstitial fibrosis with inflammatory cells infiltration were seen in HS. While the lesions in WM and BSJYD were slighter than of LS. Renal interstitial injury score showed that BSJYD can reduce renal pathology damages. HS, WM and BSJYD were respectively scored (1.77±0.20),(0.84±0.22),(1.11±0.22). as compared with the HS, WM and BSYJD were significantly lowered (P<0.05); As compared with WM, there was no difference in BSJYD (P=0.384).(4) In the mRNA expression of TGF β1, Smad2, Smad3, Smad7and CTGF:①In the mRNA expression of TGF β1, as compared with LS, HS, WM and BSJYD were significantly increased (P<0.01); As compared with HS, WM and BSJYD were significantly decreased (P <0.01); As compared with WM, there was no difference in BSJYD (P=0.61).②In the mRNA expression of Smad2, Smad3, as compared with LS, HS, WM and BSJYD were significantly increased (P<0.01); As compared with HS, WM and BSJYD were significantly decreased (P<0.01); As compared with WM, p-Smad2, p-Smad3in BSJYD was significantly elevated (P<0.01).③In the mRNA expression of Smad7, as compared with LS, HS, WM and BSJYD were significantly decreased (P<0.01); As compared with HS, WM and BSJYD were significantly increased (P<0.01); As compared with WM, there was no difference in BSJYD (P=0.83).④In the mRNA expression of CTGF, as compared with LS, HS, WM and BSJYD were significantly increased (P<0.01); As compared with HS, WM and BSJYD were significantly decreased (P<0.01); As compared with WM, CTGF in BSJYD was significantly elevated (P<0.05).(5) In the protein expression of TGF β1, p-Smad2/3, Smad7and CTGF:①In the protein expression of TGF β1, as compared with LS, HS, WM and BSJYD were significantly increased (P<0.01); As compared with HS, WM and BSJYD were significantly decreased (P <0.01); As compared with WM, there was no difference in BSJYD (P=0.86).②In the protein expression of p-Smad2/3, as compared with LS, HS, WM and BSJYD were significantly increased (P<0.01); As compared with HS, WM and BSJYD were significantly decreased (P<0.01); As compared with WM, p-Smad2/3in BSJYD was significantly elevated (P<0.01).③In the protein expression of Smad7, as compared with LS, HS, WM and BSJYD were significantly decreased (P<0.01); As compared with HS, WM and BSJYD were significantly increased (P<0.01); As compared with WM, there was no difference in BSJYD (P=0.82).④In the protein expression of CTGF, as compared with LS, HS, WM and BSJYD were significantly increased (P<0.01); As compared with HS, WM and BSJYD were significantly decreased (P<0.01); As compared with WM, CTGF in BSJYD was significantly elevated (P<0.05).Conclusion:(1) BSJYD could control BP, and improve the level of serum biochemical indexes, such as BUN, Scr and UA in DS.(2) BSJYD can alleviate severe pathological changes of kidney in DS, such as relieve the renal tubular epithelial cells falling off and vacuolar degeneration, alleviate renal interstitial inflammatory cells infiltrating, reduce basement membrane-like material, collagen fibers increased and plasma protein deposition, relieve lumens of renal tubules expanding and the less integrity of renal tubular basement membrane’s structure and reduction in renal interstitial fibrosis.(3) BSJYD can down-regulate the mRNA expression of TGF β1, Smad2, Smad3and CTGF, and up-regulate the mRNA expression of Smad7.(4) BSJYD can down-regulate the protein expression of TGF β1, p-Smad2/3and CTGF, as well as up-regulate the protein expression of Smad7.(5) BSJYD has a certain protective effect in DS, Its mechanism may be regulated by TGF β1/Smads signaling pathway:BSJYD might inhibit the over-expression of CTGF through down-regulation the expression of TGF β1, Smad2, Smad3, as well as up-regulation the expression of Smad7, and prevent the synthesis of collagen and extracellular matrix, thus playing the role of inhibiting renal interstitial fibrosis. |
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