OBJECTIVE: To observe the effects of acupuncture on blood pressure, fecal short-chain fatty acids (SCFAs) and toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway in spontaneously hypertensive rats (SHR), and to explore the mechanism of acupuncture for anti-hypertension.
METHODS: Twenty-four male SHR of SPF grade were randomly divided into a model group, a western medication group, an acupuncture group and a sham acupuncture group, with 6 rats in each group, and 6 male Wistar-Kyoto rats were selected as the blank group additionally. Hydrochlorothiazide solution was given by gavage in the western medication group; acupuncture was applied at bilateral \"Renying\" (ST 9) and \"Zusanli\" (ST 36) in the acupuncture group, 20 min a time; acupuncture was applied at the non-meridian and non-acupoint points close to bilateral \"Renying\" (ST 9) and \"Zusanli\" (ST 36) in the sham acupuncture group, 20 min a time. The intervention was adopted once a day for 4 weeks continuously in each group. The systolic blood pressure (SBP) of the caudal artery was measured before intervention and after 1, 2, 3 and 4 weeks of intervention. After intervention, the morphology of colonic tissue was observed by HE staining; the fecal level of SCFAs was detected by gas chromatography; the serum levels of interleukin (IL)-6, IL-1βand tumor necrosis factor-α (TNF-α) were detected by ELISA; the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was detected by Western blot.
RESULTS: Compared with the blank group, in the model group, the SBP was increased (P<0.05), significant pathological changes could be found in the colonic tissue, the fecal SCFAs level was decreased (P<0.05), the serum levels of IL-6, IL-1β and TNF-α were increased (P<0.05), the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was increased (P<0.05). Compared with the model group, the SBP after 2, 3 and 4 weeks of intervention was decreased (P<0.05), the serum levels of IL-6, IL-1β and TNF-α were decreased (P<0.05) in the acupuncture group and the western medication group; the mucosal epithelium of colonic tissue was intact, the number of intestinal glands was abundant, the fecal SCFAs level was increased (P<0.05), and the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was decreased (P<0.05) in the acupuncture group. Compared with the sham acupuncture group, the SBP after 2, 3 and 4 weeks of intervention was decreased (P<0.05), the fecal SCFAs level was increased (P<0.05), the serum levels of IL-6, IL-1β and TNF-α were decreased (P<0.05), the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was decreased (P<0.05) in the acupuncture group.
CONCLUSIONS: Acupuncture at bilateral \"Renying\" (ST 9) and \"Zusanli\" (ST 36) can effectively play an anti-hypertensive role in SHR. Its mechanism may be related to regulating fecal SCFAs level and inhibiting the TLR4/MyD88/NF-κB signaling pathway.
目的:观察针刺对自发性高血压大鼠(SHR)血压、粪便短链脂肪酸(SCFAs)及toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子κB(NF-κB)信号通路的影响,探讨针刺降压的作用机制。方法:将24只SPF级雄性SHR随机分为模型组、西药组、针刺组和假针组,每组6只;另设6只Wistar-Kyoto(WKY)大鼠为空白组。西药组予氢氯噻嗪溶液灌胃;针刺组针刺双侧“人迎”“足三里”,每次20 min;假针组针刺双侧“人迎”“足三里”附近的非经非穴点,每次20 min。均每日1次,持续4周。干预前及干预第1、2、3、4周后测量各组大鼠尾动脉收缩压(SBP);HE染色观察大鼠结肠组织形态;气相色谱-质谱联用仪检测大鼠粪便SCFAs含量;ELISA法检测大鼠血清白细胞介素(IL)-6、IL-1β和肿瘤坏死因子-α(TNF-α)含量;Western Blot法检测大鼠肠系膜动脉中TLR4、MyD88和NF-κB p65蛋白表达。结果:与空白组比较,模型组大鼠SBP升高(P<0.05),结肠组织有明显病理变化,粪便SCFAs含量降低(P<0.05),血清IL-1β、IL-6和TNF-α含量升高(P<0.05),肠系膜动脉中TLR4、MyD88、NF-κB p65蛋白表达升高(P<0.05)。与模型组比较,针刺组和西药组大鼠干预2、3、4周后SBP降低(P<0.05),血清IL-1β、IL-6和TNF-α含量降低(P<0.05);针刺组大鼠结肠组织黏膜上皮完整,肠腺数量丰富,粪便SCFAs含量升高(P<0.05),肠系膜动脉中TLR4、MyD88、NF-κB p65蛋白表达降低(P<0.05)。与假针组比较,针刺组干预2、3、4周后SBP降低(P<0.05),粪便SCFAs含量升高(P<0.05),血清IL-1β、IL-6和TNF-α含量降低 (P<0.05),肠系膜动脉中TLR4、MyD88、NF-κB p65蛋白表达降低(P<0.05)。结论:针刺双侧“人迎”“足三里”可有效降低SHR血压,其机制可能与调节粪便SCFAs含量、抑制TLR4/MyD88/NF-κB信号通路有关。.