The Effect Of Renal Denervation On Hypothalamus P38MAPK And P65NFκB Signal Pathwayin SHR Rats

BackgroundThe overactivity of sympathetic nervous system is one of the main mechanisms of hypertension. Thus, inhibition of the enhanced sympathetic nervous activity is one of the targets for the treatment of hypertension. Renal denervation can lower blood pressure by selectively blocking thesympathetic nervous located in the adventitial of the renal artery. However, the central mechanisms and the download signalingpathway for renal denervationis still unclear now.ObjectivesThis study is to observe the chang of hypothalamic AngII,AT1 R, p38 MAPK and p65NFκBbefore and after renal denervation on spontaneously hypertensive rats, to explore the effect of renal denervation on MAPK and NFκB signaling pathway.Methods 36 SHR rats were divided into three groups randomly: SHR baseline group, RDN group and sham group. Choose the same age WKY rats as the baseline control group(WKY group, n = 12). The SHR baseline group(n = 12) and WKY group were sacrificed after two weeks fed in 12 weeks. And in 12 weeks,rats in RDN group and sham group were given RDN or sham operation, then sacrificed respectively 1 week and 6 weeks after RDN(D1 group, n = 6; D6 group, n = 6); and 1 week and 6 weeks after sham operation(S1 group, n = 6; S6 group, n = 6), kidney and hypothalamus were collected for examinition. The content of plasma S100 B, NSE, kidney NE and hypothalamic AngII were determined by ELISA. The protein expression of p38 MAPK, p-p38 MAPK and p65NFκB in hypothalamus were determined by Westem-Blot and the mRNA expression of AT1 R and p38 MAPK in hypothalamus were detected by real-time PCR.Results1.In aspect of heart rate and body weight, there was no difference between SHR blank group and WKY group(p>0.05).In SHR blank group, the level of blood pressure; the content of hypothalamic Ang II, kidney NE, plasma NSE and S100 B and the expression of AT1 R, p38 MAPK, p-p38 MAPK and p65NFκB increased significantly compared with WKY group(p<0.05).2.In aspect of heart rate and body weight, there was no difference between SHR group and sham groupin the same time(p>0.05); the blood pressure in D1 group decresed significantIy compared with the S1 group(p<0.05); the blood pressure in D6 group incresed significantIy compared with the D1 group(p<0.05), and there was no difference compared with the S6 group(p>0.05).3.The level of plasma S100 B, NSE in D1 group increased significantIy compared with the S1 group(p<0.05); but in D6 group there was no difference compared with the S6 group(P>0.05).4.The level of kidney NE and hypothalamic AngII, the expression ofAT1 R, p38 MAPK, p-p38 MAPK, p65NFκB in hypothalamic in D1 group decresed significantIy compared with the S1 group(p<0.05); In D6 group, they were still lower than that of the S6 group(p<0.05), but there was no difference compared with the SHR blank group(P>0.05).Conclusions1. Renal sympathetic denervation can significantly decrease the level of NE in kidney and can effectively lower blood pressure ofSHR rats in a short term;2. Renal sympathetic denervation can significantly increase the level of plasma NSE and S100B; and there in a negatively correlation between plasma NSE, S100 B with kidney NE;3. Renal sympathetic denervation can inhibited the renin- angiotensin system in hypothalamus;4. Renal sympathetic denervation can suppression the p38 MAPK and p65 NFκB signal pathway, to participate in central antihypertensive effect of RDN.