| Objective: Hypertension has become a global epidemic disease.It has been studied that the activation of sympathetic nervous system and rennin-angiotensin-aldosterone system(RAAS)plays an important role in the occurrence and development of hypertension.Application of drugs can inhibit the excessive activation of sympathetic nerve and RAAS system to lower blood pressure.But it is also need to persist in long-term treatment,as well as existing drug side effects.In recent years,domestic and foreign research shows that using catheter-based renal denervation by radiofrequency ablation(RFA)can effectively inhibit the excessive activation of sympathetic and RAAS system to lower blood pressure,and to achieve the goal of treating refractory hypertension,and then to benefit the target organ.Because this is a new technology in the treatment of refractory hypertention,and it is a breakthrough and innovation in traditional methods.So a large number of basic and clinical studies are needed to demonstrate its safety and effectiveness.It has been studied that this technique can make the blood pressure decrease nearly 40 mmHg in spontaneously hypertensive rat(SHR).This study aims to observe the change of blood pressure and the influence of target organ before and after the renal denervation surgery in SHR,and to investigate the effects of blood pressure intervention effect and related target organ,and then to provide a new therapeutic method for the treatment of primary hypertension.Methods: 12 weeks of age young SHR(n=24)as the research object,combined with the application of surgical resection and chemical ablation method(a solution of 10 % phenol in ethanol)to establish a model of renal denervation.They were randomly divided into renal denervation group(RDN group)and sham operation group(Sham group).The same week old WKY rats(n=12)as the baseline control group.Blood pressure and body weight was measured before surgery and per week after surgery to put to death the day before.Four rats were randomly sacrificed at one week,eight weeks,and twelve weeks after surgery in three different groups,and the plasma,heart,kidney and aorta were collected.The content of norepinephrine(NE)and angiotensin II(Ang II)in plasma to determine by ELISA method.Calculation of left ventricular weight/body weight(LVMI);the myocardial tissues were stained with HE to observe the morphology of left ventricular myocardial cells;the expression of ?-MHC and COL I protein in left ventricular to determine by Western Blot method.Kidney tissues were stained with HE to observe the renal morphology,and were stained with PAS to observe the degree of glomerular sclerosis;the expression of COL I protein in kidney to determine by Western Blot method.The aorta was stained with HE to observe the aortic morphology.Luminal radius(LR)and Media thickness(MT)were measured by Image-Pro Plus6.0,and to calculate MT/LR.SPSS version 13.0 was employed for statistical analysis.Data were expressed as mean ± standard deviation(?x±s).Means in two groups were compared with t test,and among different groups were compared with single factor analysis of variance(one way ANOVA).Repeat measurement of multiple times were compared with repeated measures analysis of variance.A value of P<0.05 was considered statistically significant.Results:1 The comparison of body weightThere were no statistical difference in body weight between RDN group and Sham group before surgery and per week after surgery(P>0.05).But the body weight of RDN group and Sham group were lower than WKY group before surgery and per week after surgery(P<0.05).2 The measurement of systolic blood pressure(SBP)There were no statistical difference in SBP between RDN group and Sham group before surgery(175.0±2.8mmHg vs.174.5±2.7mmHg)(P>0.05),and they were larger than WKY group(132.2±4.2mmHg)(P<0.05).The SBP of RDN group was lower than Sham group at one to five weeks after surgery(145.3±1.6mmHg vs.181.0±3.7mmHg,154.8±2.9mmHg vs.190.4±7.7mmHg,160.3±4.5mmHg vs.196.0±6.4mmHg,166.2±4.3mmHg vs.203.6±8.0mmHg,184.6±3.2mmHg vs.201.5±9.0mmHg)(P<0.05).There were no statistical difference in SBP between RDN group and Sham group at six weeks after surgery and later(P>0.05).The SBP of Sham group at one week after surgery was slightly higher than before surgery(181.0±3.7mmHg vs.174.5±2.7mmHg)(P<0.05);the SBP of Sham group at two weeks after surgery(190.4±7.7mmHg)was no statistical difference with at one week after surgery(P>0.05);the SBP of Sham group at three weeks after surgery(196.0±6.4mmHg)was slightly higher than at two weeks after surgery(P<0.05);the SBP of Sham group had continued at a high level and was no significant change at three weeks after surgery and later(P>0.05).The SBP of RDN group and Sham group were higher than WKY group at the same time(P<0.05).The SBP of WKY group was no statistical difference at each time(P>0.05).3 The change of the content of NE in plasmaThere were no statistical difference in the content of NE in plasma between RDN group and WKY group at one week after surgery(169.1±3.8pg/ml vs.170.4±3.2pg/ml)(P>0.05),and they were significantly lower than Sham group(222.3±4.2pg/ml)(P<0.05).There were no statistical difference in the content of NE in plasma between RDN group and Sham group at eight weeks after surgery(231.4±3.8pg/ml vs.234.5±2.7pg/ml)(P>0.05),and they were higher than WKY group at the same time(171.3±5.6pg/ml)(P<0.05).There were no statistical difference in the content of NE in plasma between RDN group and Sham group at twelve weeks after surgery(238.6±2.7pg/ml vs.241.1±5.9pg/ml)(P>0.05),and they were higher than WKY group at the same time(171.4±5.4pg/ml)(P<0.05).4 The change of the content of Ang II in plasmaThere were no statistical difference in the content of Ang II in plasma between RDN group and WKY group at one week after surgery(90.0±1.4pg/ml vs.89.3±2.4pg/ml)(P>0.05),and they were significantly lower than Sham group(171.9±2.8pg/ml)(P<0.05).There were no statistical difference in the content of Ang II in plasma between RDN group and Sham group at eight weeks after surgery(174.5±2.0pg/ml vs.173.9±1.5pg/ml)(P>0.05),and they were higher than WKY group at the same time(90.1±3.2pg/ml)(P<0.05).There were no statistical difference in the content of Ang II in plasma between RDN group and Sham group at twelve weeks after surgery(173.5±1.9pg/ml vs.173.3±2.8pg/ml)(P>0.05),and they were higher than WKY group at the same time(90.1±2.9pg/ml)(P<0.05).5 The change of LVMIThere were no statistical difference in LVMI between RDN group and Sham group at one,eight and twelve weeks after surgery(P>0.05),but they were higher than WKY group at the same time(P<0.05).6 The myocardial tissues were stained with HE to observe the change of myocardial cells morphology in different groupsIn WKY group,the size of myocardial cells were normal and cells arranged in neat,myocardial nucleus were oval and located in the center of cells,myocardial interstitium was no obvious hyperplasia at one,eight and twelve weeks after surgery.In RDN and Sham group,the myocardial cells were presented the different degrees of damage at one,eight and twelve weeks after surgery.And it was showing that myocardial hypertrophy and disordered,myocardial interstitial edema,part of the myocardial cells lysis,the surrounding structure was not clear.7 The expression of ?-MHC and COL I protein in left ventricular to determine by Western Blot methodThe expression of ?-MHC in RDN group and Sham group were no statistical difference at one,eight and twelve weeks after surgery(P>0.05),and were lower than that in WKY group at the same time(P<0.05).The expression of COL I in RDN group and Sham group were no statistical difference at one,eight and twelve weeks after surgery(P>0.05),and were higher than that in WKY group at the same time(P<0.05).8 Renal tissues were stained with HE to observe the renal morphology,and were stained with PAS to observe the degree of glomerular sclerosisIn WKY group,the glomerular size and morphology were normal and renal tubular arranged regularly at one,eight and twelve weeks after surgery.In RDN and Sham group,individual glomerular was presented atrophy and hardening,the part of the glomerular was presented compensatory hypertrophy,the part of the renal tubular was presented atrophy at one,eight and twelve weeks after surgery.9 The expression of COL I protein in kidney to determine by Western Blot methodThe expression of COL I in RDN group and Sham group were no statistical difference at one,eight and twelve weeks after surgery(P>0.05),and were higher than that in WKY group at the same time(P<0.05).10 The aorta was stained with HE to observe the change of aortic morphology in different groups and the measurement of relative indexesIn WKY group,there were no statistical difference in aortic luminal radius(LR),media thickness(MT)and MT/LR at one,eight and twelve weeks after surgery(P>0.05),and LR and MT were normal,the vascular wall cells arranged regularly.In Sham group,LR,MT and MT/LR increased gradually at one,eight and twelve weeks after surgery(P<0.05),and the vascular wall cells arranged irregularly,the cell density decreased.In RDN group,LR,MT and MT/LR increased gradually at one,eight and twelve weeks after surgery(P<0.05),and which were no statistical difference with in Sham group(P>0.05)at the same time,and both of them were higher than in WKY group at the same time(P<0.05).Conclusion:1 The renal denervation had no effect on the growth of rats,but long-term hypertension prevented the growth of rats.2 The renal denervation could decrease in blood pressure,especially in the postoperative one week,but its antihypertensive effect could not be stable and lasting.3 The mechanism of lowering blood pressure in renal denervation is the reduction of NE secretion and the inhibition of the RAAS system.4 Due to the renal denervation only can reduce blood pressure for a short while,but can not be sustained and stable,so the high blood pressure on the target organ damage has not been significantly improved. |
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