| Objective: To observe the effect of YangGanYiShui Granule on early renal damage ofessential hypertension patients in the index of clinical effect, ambulatory bloodpressure, urine MA, β2-MG and plasma ET, NO levels, as well as the influence onspontaneously hypertensive rats (SHR) blood pressure, blood Scr, BUN, renalpathological urine protein, enzyme, collagen content of renal tissue (MMP-1, TIMP-1),the renal expression of p-JAK1, p-JAK2, p-STAT1, p-STAT3protein level and STAT1,STAT3expression of mRNA,And to expound the pathogenesis of early renal damagein essential hypertension, to evaluate the effect of YangGanYiShui granule’s links andchannels, to explore its therapeutic mechanism in order to provide scientific andreasonable theoretical basis for early renal damage in YangGanYiShui granule forprevention and treatment of hypertension.Methods: Clinical observation: We select70patients with early renal damage ofhypertension patients who accord with syndrome differentiation of traditional Chinesemedicine, And randomly divide them into treatment group and control group. The twogroups were given conventional therapy of depressurization. At the sametime,treatment group was treated with YangGanYiShui granule. The two groups weretreated for4weeks. And respectively to observe the change of blood pressure,TCMsyndrome integral value and dynamic, and to detecte the changes of urinary MA, β2-MG and plasma ET, NO level before and after4weeks’treatment.Animal experiment:SHR No.64were randomly divided into4groups, yangganyishuiparticles of high and low dose treatment group, Bella Plymouth control group, modelgroup,16in each group, while16WKY rats were selected as a control.1.By the end ofthe arterial pulse measurement before the experiment, experiment6weeks,12weeksof experiment tested the rats blood pressure;2.Using automatic biochemical analyzerbefore the experiment, after the experiment measured the rats serum creatinine andblood urea nitrogen;3. measured by radioimmunoassay before the experiment, after the experiment rats in each group MA in urine and urinary β2-microglobulin;4.made PASstaining after the experiment to make the rats of kidney specimens, and in lightmicroscope,to observe the pathological changes of renal tissue.5.Immunohistochemical method was used to detect MMP-1, TIMP-1content of renaltissue；6. Detected by Western blot after the test the rats kidney, p-JAK1、p-JAK2、p-STAT1、p-STAT3expression;7. By RT-PCR testing renal cortex of rats STAT1、STAT3mRNA expression after experiment;8. using SPSS17.0software package forstatistical analysis.Results: Clinical observation:1.Two groups of TCM syndrome score no significantdifference (p>0.05) before treatment, after treatment of the TCM syndromes treatmentgroup than in the control group decreased significantly (p<0.01).2.Compared beforeand after treatment, two groups of24hSBP, DBP decreased significantly (p<0.01),24hSBP before treatment, DBP had no significant difference, but the treatment group,24h systolic pressure (SBP) decreased significantly than the control group (p<0.05).3.In two groups before treatment MA, β2-MG no significant difference (p>0.05). Aftertreatment, the two indexes were significantly lower than the control group(p<0.05).4.Before treatment, two groups of ET, NO no significant difference (p>0.05).After treatment, two groups of ET were significantly decreased (p<0.01). Treatmentand after treatment in group ET compared with the control group decreased moresignificantly, and has significant difference (p<0.05). After treatment, two groups ofNO were significantly increased (p<0.01). And NO compared with the control groupincreased more significantly, and has significant difference (p<0.05).Animal experiment:1.SHR in each group before the experiment blood pressure wassignificantly higher than that of WKY rats (P <0.01); experiment with the model grouprats showed increased age of increased blood pressure, and YGYS particles of high andlow dose treatment SHR group and Bella plymouth Group were tended to increaseblood pressure decreased, and blood pressure amplitude in the three similar (P>0.05),but YGYS high dose group particles biggest buck.2. Treatment before and after the model group, SHR blood Scr, BUN was significantly higher than WKY rats (P <0.01);treatment groups after treatment could reduce the SHR blood Scr, BUN (P <0.01), butcompared to the three no significant difference (P>0.05).3. Before and after treatmentin each group SHR urinary MA, urinary β2-MG was significantly higher than WKYrats (P <0.01); SHR treatment groups after treatment of urinary MA, urinary β2-MGlevels were lower compared with the model group significant difference (P <0.01);Bettwen low-dose yangganyishui group and medicine group the difference was notstatistically significant (P>0.05), but the high dose group with low dose group ofChinese medicine and western medicine group was significantly different compared (P<0.05, P <0.01).4. Test model group compared with the normal group was theperformance of renal sclerosis, and the treatment performance of small renal sclerosis.The model group compared with normal group and MMP-1expression decreaseddistribution area reduced, the two groups had statistical significance between theintegral optical density difference (P<0.05); The low-dose group integral opticaldensity compared with the model group, the difference was not statistically significant(P>0.05); Expression of the group of Western medicine, MMP-1of high dose groupcompared with the model group was significantly enhanced and the area increased,there was statistically significant difference between the integral optical density (P <0.05). Expression of TIMP-1in model group compared with normal group increased,two groups of integral optical density value comparison, the difference was statisticallysignificant (P <0.05); The western medicine group and the low-dose group integraloptical density compared with the model group, the difference was not statisticallysignificant (P>0.05); expression of Chinese medicine high dose group of TIMP-1ishigher than that of model group decreased, compared two groups of integral opticaldensity, the difference was statistically significant (P <0.05).6. Compared with thecontrol group, the expression of model group rats, p-JAK1、p-JAK2、p-STAT1andp-STAT3in glomerular protein were increased (all P <0.01). Compared with themodel group, high dose Chinese medicine group of glomeruli of rats with p-STAT1 and p-STAT3expression was down regulated (p<0.05). The expression of SHR in renalcortex of STAT1model group, STAT3mRNA was significantly higher than that ofWKY rats (P <0.01); The treatment group can significantly reduce the renal cortexSTAT1, SHR STAT3mRNA (P <0.01), The low dose of Chinese medicine group andWestern medicine group had no significant difference (P>0.05), but both with highdose group compared with significant difference (P <0.05, P <0.01).Conclusion:1.YangGanYiShui granule can obviously reduce the early renal damage inhypertensive patients with urinary MA excretion, beta2-MG, regulation of circadianrhythm of blood pressure, decreasing the level of ET, increase the level of NO,preliminary results show the party may by regulation between ET and NO, improvingglomerular sclerosis.2.YangGanYiShui granule could reduce the synthesis anddegradation of ECM by regulating the balance between MMP-1/TIMP-1, so as toreduce or inhibit the renal tubular interstitial fibrosis purpose.3. Mechanism of earlyrenal damage of YangGanYiShui granule in prevention and cure of hypertension inaddition to improve the hemodynamics factors, may also inhibit the JAK1, through theJAK/STAT pathway JAK2and STAT1and the phosphorylation of STAT3, inhibit orblock the activation of the JAK/STAT pathway, the transcription and expression andeffect of inflammatory cytokines and profibrotic genes, reduces the synthesis andaccumulation of ECM, improve glomerular sclerosis, occurrence, development processinvolved in early renal damage in essential hypertension. |
PDF Full Text Request