| Objective: To observe the effect of tandospirone citrate on tail artery systolic blood pressure;to investigate the repair effect of tandospirone citrate on vascular endothelial function;to study on anti-hypertensive molecular mechanism of tandospirone citrate,further observing whether tandospirone has a protective effect on the heart,brain,kidney and other organs;to provide scientific experimental data and theoretical basis for clinical syndrome differentiation treatment.Methods : 40 SHR aged 9 weeks were divided into SHR model group(10ml×kg-1×d-1 distilled water,n=8),levamlodipine group(L Group,2.5mg×kg-1×d-1,n=8),tandospirone citrate in high dose group(high dose group,40mg×kg-1×d-1,n=8),tandospirone citrate in middle dose group(middle dose group,20mg×kg-1×d-1,n=8),tandospirone citrate in low dose group(low dose group,10mg×kg-1×d-1,n=8)by table of random number.Another 8 normal arterial pressure WKY at the same age were choosed as blank control group(WKY group,10ml×kg-1×d-1 distilled water,n=8).Systolic blood pressure(SBP)was measured by automatic non-invasive blood pressure measuring system BP-600 A before single administration and then separately at 30,60,90,120,180,240 minutes after single administration.With successive administration for28 d,SBP was measured at 1h after each administration for every 7d undergoing chronic dose.After continuous treatment for 28 d,fasting and free drinking water for 24 hours,taking abdominal aorta blood,to collecte plasma andserum,which for nitrate reduction method to detect NO content and ELISA to detect ET,Renin,Ang II and NE content.Then quickly take the left kidney,and detect the expression of ACE and AT-1R gene fluorescent quantitative PCR;The right ones were taken into the EP tube with 15 ml 10% formalin to fixate,and the pathological changes were detected by HE staining.All rats' hearts were quickly removed,fixating with 15 ml 10% formalin,and the pathological changes were detected by HE staining.The brains of all rats were quickly removed.Separate locus coeruleus in randomly selected 4 rats in each group,detect the expression of alpha 1,alpha 2 and beta 1 and beta 2 gene in locus coeruleus using fluorescent quantitative PCR;the rest of the brains fixate with15 ml 10% formalin for HE staining method to detect pathological changes.The data was analyzed by SPSS 22.0 factor analysis of variance,comparison between groups using LSD analysis.The results were presented as X±S,and P(27)0.05 was thought to have significant differences.Results:(1)Compared with the normal group of WKY,The systolic blood pressure(SBP)was significantly increased in the other groups(P<0.01);30min after a single dose,compared with the model group,the SBP of high dose group,middle dose group and low dose group decreased significantly,there was significant difference except the middle groups(P<0.05),and the high dose group had a very significant difference(P<0.01),and the antihypertensive effect lasted until 240Min(P<0.05 or P<0.01);The blood pressure of the L group continued to decline after dose,and can be regulated to 240min(P<0.05 or P<0.01).Compared withthe L group,the antihypertensive effect of the high dose group was comparable,but the effect of another two group was relatively weak.Successive administration for 7 days,compared with the model group,the SBP of the high dose group and middle dose group was significantly lower(P<0.01);Successive administration for 14 days,There was significant difference between the high dose group and the model group(P<0.01),and the difference in the middle dose group(P<0.05);Continuous dose of 21 d and 28 d,the middle dose group and low dose group was not obvious,while the high dose group had significant antihypertensive effect(P<0.01).The blood pressure continued to decline after the dose,and can be regulated to 28d(P<0.01);Compared with the L group,the antihypertensive effect of the high dose group was similar,but in the middle and low dose group,the blood pressure was lower.(2)The serum NO level in SHR model group was significantly lower than that in group WKY(P<0.01);The content of serum NO in L group and high dose group was significantly higher than that in the SHR group(P<0.01);The content of serum NO in Moderate and low dose group also increased to a certain extent,but the difference was not statistically significant.(3)The plasma ET level in SHR model group was higher than that in WKY group(P<0.05);The content of ET in plasma of L group and high dose group were lower than that of SHR group(P<0.05);middle and low dose group were lower than model group,but the difference was not statistically significant.(4)The plasma Renin level in SHR model group was significantly higher than that in group WKY(P<0.01),Thecontent of Renin in serum of rats in L group was significantly lower than that in SHR group(P<0.01),The serum Renin levels in the high,middle and low dose groups were also lower than those in the model group(P<0.01 or P<0.05),and the difference was statistically significant.(5)The plasma NE level in SHR model group was higher than that in group WKY(P<0.05),The content of NE in the serum of the rats in the L group was lower than that in the SHR model group(P<0.05),the content of NE in the high,middle and low dose group was significantly lower than that in the SHR model group(P<0.05).(6)The plasma Ang II levels in SHR model group were higher than those in group WKY(P<0.05),The contents of plasma Ang II in the L group and high dose group were lower than those in the SHR group(P<0.05),The middle and low dose group was higher than that in SHR model group,but the difference was not statistically significant.(7)Compared with WKY group,the expression of ACE and AT1 R in renal tissue of SHR model group was significantly higher,The expression of ACE and AT1 R in high,middle and low dose group was lower than that in model group,but the difference was not statistically significant.(8)Compared with WKY group,the expression of ?1-AR and ?1-AR gene was significantly increased in locus caeruleus of SHR model group.The expression of the two gene in high,middle and low dose group was lower than that in model group,but the difference was not statistically significant;compared with the WKY group,the expression of ?2-AR of kidney in SHR model group was lower.After treatment,the gene expression of each dose group increased,butthe difference was not statistically significant.There was no significant trend in the expression of ?2-ARgene in each group.(9)HE staining of heart,brain and kidney showed that each dose group of tandospirone had different degrees protection of them,Among them,the protection of heart and kidney was the most obvious.Conclusion:1.Tandospirone citrate showed a better depressurization effect on SHR tail artery systolic blood pressure,After 28 days of high dose treatment,the stable phase was reached and the depressurization effect was similar to L group.2.Tandospirone citrate may regulated the release of vascular endothelial vasomotor factor NO and ET and improve the dysfunction of vascular endothelial in hypertension process.3.Tandospirone citrate may regulated the content of Renin,Ang II,and NE in RAS system to achieve the role of anti-hypertension.4.Tandospirone citrate on renal ACE and AT1 R gene regulation is not obvious,but probably by regulating sympathetic nerve,and lower blood pressure.5.Tandospirone citrate can effectively improve the pathological morphology of heart and kidney in SHR,play the role of heart and kidney protection in heart and kidney. |
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