Modulation of macrophage polarization and nephroprotective effects of acupuncture in SHR kidneys explored based on the TLR4/NF-κB pathway
Objective To observe the effects of acupuncture manipulation on blood pressure and renal inflammatory environment in spontaneously hypertensive rats(SHR),and to elucidate the mechanism of antihypertensive and nephroprotective effects of the manipulation.Methods 36 male SHRs were randomly divided into 3 groups including the model group(SHR group),the twirling reducing manipulation group(TRD group)and the twirling reinforcing manipulation group(TRF group).In addition,12 WKY rats were used as the control group(WKY group).The TRD and the TRF groups were subjected to twirling reducing manipulation and twirling reinforcing manipulation in LR3 respectively,once a day for two weeks,with one day of rest in between the two weeks.During the intervention period,we measured the blood pressure of the rats using the tail pressure method.After two weeks,the serum and kidney tissues of rats in each group were collected,and the concentrations of norepinephrine(NE)and Angiotensin Ⅱ(AngⅡ)in serum and the contents of interleukin(IL)-1 β and IL-10 in kidneys were detected by Elisa method;the expressions of Toll-like receptor 4(TLR4),nuclear factor-κB(NF-κB),cluster of differentiation(CD)86 and CD206 proteins in kidneys were detected by Western blot method;and morphological changes of kidneys were observed by HE staining.Results(1)Compared with the WKY group,the blood pressure of rats in the SHR group was significantly increased(P<0.01),serum NE and AngⅡ concentrations were significantly increased(P<0.01),and the content of TLR4,NF-κB,CD86,IL-1 β in kidney was significantly increased(P<0.01)and the content of CD206 and IL-10 was significantly decreased(P<0.01).The results of HE staining showed that SHRs appeared irregular renal tubular and glomerular morphology,with the presence of inflammatory cell infiltration.(2)Compared with SHR group,blood pressure was significantly decreased in the TRD group and the TRF group(P<0.01),serum NE and AngⅡ concentrations were significantly decreased(P<0.01).The expression of TLR4,NF-κB,CD86 the kidney was significantly decreased(P<0.01),and the concentration of IL-1 β was decreased(P<0.05,P<0.01),and the content of CD206 and IL-10 was significantly increased(P<0.01).The morphology of renal tubules and glomeruli was normal,and a small amount of inflammatory cell infiltration was present.(3)Compared with the TRD group,the TRF group had higher blood pressure(P<0.05),and changes in serum concentrations of NE,AngⅡ,and renal levels of TLR4,NF-κB,CD86,CD206,IL-1 β,and IL-10,with statistically significant differences(P<0.05 or P<0.01).Conclusion Acupuncture at LR3 with twirling reinforcing and reducing manipulation inhibited renal inflammation by decreasing sympathetic excitability to lower AngⅡ and inhibiting TLR4/NF-κB pathway to regulate macrophage polarization to exert both antihypertensive and nephroprotective effects,and the twirling reducing manipulation was more effective than the twirling reinforcing manipulation.
Taichong(LR3)acupuncturetwirling reinforcing and reducing acupuncture ma-nipulationsmacrophage polarizationTLR4/NF-κB pathwayspontaneous hypertensionrenoprotectionsympathetic nervous system