首页|针刺调节JNK-MCP1通路减轻自发性高血压大鼠脑白质病变模型室旁核炎症损伤机制研究

针刺调节JNK-MCP1通路减轻自发性高血压大鼠脑白质病变模型室旁核炎症损伤机制研究

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目的:探讨针刺"降压方"腧穴对自发性高血压大鼠(SHR)双血管逐渐闭塞(2VGO)模型下丘脑室旁核(PVN)炎症损伤的治疗作用,并从c-Jun 氨基末端激酶(JNK)/单核细胞趋化蛋白-1(MCP-1)通路探讨其相关机制.方法:SHR大鼠30只,随机选10只仅分离双侧颈总动脉,作为假手术组;其余20只SHR大鼠植入血管收缩器渐缩环以缩窄颈总动脉,制作双血管渐闭SHR脑白质病变(SHR-2VGO)模型,造模2周后剔除运动功能受损大鼠,最终造模成功的18只SHR-2VGO大鼠随机分为模型组、针刺组各9只.假手术组、模型组与针刺组以相同的方式固定,同时针刺组予腧穴"降压方"针刺,1次/d,每次留针30 min,干预疗程为4周.采用无创血压测量系统,每周对大鼠进行收缩压、舒张压测量,进行针刺降压效果的评估.苏木伊红染色和尼氏染色用于评估各组大鼠室旁核后部(PVP)发生的组织病理变化,免疫荧光法检测各组大鼠PVP脑区JNK、MCP1表达,实时荧光定量 PCR 检测各组大鼠室旁核前部(PVA)肿瘤坏死因子-α(TNF-α)和白介素6(IL-6)mRNA相对表达量.结果:在针刺前及观察期第1、2、3、4周,与假手术组比较,模型组大鼠收缩压和舒张压显著升高(P<0.05);在观察期第3、4周,与模型组比较,针刺组大鼠收缩压和舒张压显著降低(P<0.05).假手术组PVP脑区神经分泌大、小细胞分布规律,两类细胞在模型组呈分布稀疏、形态不规则,两类细胞在针刺组呈交叉排布的形态.假手术组大鼠PVP脑区尼氏小体数量较丰富,体积较大;模型组PVP脑区尼氏小体数量明显下降,神经细胞受到明显破坏;针刺组尼氏小体体积较小,但与模型组比较数量明显增加.与假手术组比较,模型组PVP区JNK-MCP1荧光强度显著升高(P<0.05);与模型组比较,针刺组JNK-MCP1荧光强度降低(P<0.05).与假手术组比较,模型组PVA组织中TNF-α mRNA和IL-6 mRNA水平明显升高(P<0.05);与模型组比较,针刺组PVA脑区TNF-α mRNA和IL-6 mRNA水平明显下降(P<0.05).结论:针刺"降压方"腧穴可缓解SHR-2VGO大鼠PVN组织病理损伤,增加尼氏小体数量,通过针灸调控JNK-MCP1通路缓解SHR-2VGO大鼠室旁核炎症损伤.针灸缓解高血压脑白质损伤相关神经炎症是值得研究的潜在治疗策略.
Mechanism research of reduction of inflammatory injury in the paraventricular nucleus in spontaneously hypertensive rats with white matter lesions by the effect of acupuncture on regulating the JNK-MCP1 pathway
Objective:To investigate the therapeutic effect of acupuncture at"jiangyafang"acupoint on inflammatory injury of paraventricular nucleus(PVN)in spontaneously hypertensive rats(SHR)in the mode of two blood vessels gradual occlusion(2VGO),and to explore its related mechanism from the angle of c-Jun N-terminal kinase(JNK)and monocyte chemotactic protein-1(MCP-1)pathways.Methods:30 SHR rats were selected.,10 SHR rats were randomly selected to separate only bilateral common carotid arteries as sham-operated group;another 20 SHR rats were implanted with vasocon-strictor reducing rings to narrow the common carotid arteries,and SHR white matter lesions model with two blood vessels gradual occlusion(SHR-2VGO)was made.The rats with impaired motor function were excluded after 2 weeks of model se-lection.,18 SHR-2VGO rats after successful molding were randomly divided into model group(9 rats)and acupuncture group(9 rats).The rats in the sham-operated group and the model group were fixed in the same way as the rats in the acu-puncture group.At the same time,the rats in the acupuncture group were acupunctured at"jiangyafang"acupoint for once a day,30 min each time,and the intervention course was 4 weeks.The systolic and diastolic blood pressure of rats were mea-sured weekly by non-invasive blood pressure measurement system,and the antihypertensive effect of acupuncture was evaluated.The histopathological changes of PVN in each group were evaluated by HE staining and Nissl staining.The ex-pressions of JNK and MCP1 in PVN in each group were detected by immunofluorescence method.Real-time fluorescence quantitative PCR was used to detect the relative expression of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA in PVN tissue of rats in each group.Results:Compared with sham-operated group,systolic blood pressure and dia-stolic blood pressure of rats in model group were significantly increased before acupuncture and at the 1st,2nd,3rd and 4th week of observation period(P<0.05);at the 3rd and 4th week of the observation period,compared with the model group,the systolic blood pressure and diastolic blood pressure of rats in the acupuncture group were significantly decreased(P<0.05).The distribution of large and small neurosecretory cells in the encephalic region of PVN of the sham-operated group was regular.The two types of cells showed sparse distribution and irregular shape in the model group,while the two types of cells showed cross arrangement in the acupuncture group.The number of Nissl bodies in the encephalic region of PVN of rats in the sham-operated group was abundant and the volume was large;in the model group,the number of Nissl bodies in the PVN was significantly decreased,and the nerve cells were significantly damaged;the volume of Nissl bodies in the acu-puncture group was smaller,but the number was significantly increased compared with that of the model group.Compared with that of the sham-operated group,the fluorescence intensity of JNK-MCP1 in PVN was significantly increased in the model group(P<0.05);compared with that of the model group,the fluorescence intensity of JNK-MCP1 was decreased in the acupuncture group(P<0.05).Compared with those of the sham-operated group,the TNF-α and IL-6 mRNA levels in PVN tissues in the model group were significantly increased(P<0.05);compared with those of the model group,the relative expression levels of TNF-α and IL-6 mRNA in PVN tissues in the acupuncture group were significantly decreased(P<0.05).Conclusion:Acupuncture at"jiangyafang"acupoint can alleviate the pathological injury of PVN in SHR-2VGO rats,increase the number of Nissl bodies,and alleviate the inflammatory injury of PVN in SHR-2VGO rats by regulating JNK-MCP1 pathway.Acupuncture alleviates neuroinflammation associated with hypertensive white matter lesions,which is a potential treatment strategy worth studying.

spontaneous hypertensionwhite matter lesions"jiangyafang"acupointinflammatory injury in PVNJNK-MCP1 pathway

董爱爱、杨端蓉、王文瑞、任佳、崔依依、金晓飞、郝日雯、王海军、李丽、冀来喜

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山西中医药大学第二临床学院,山西 晋中 030619

河北省保定市第一中医院,河北 保定 071000

山西省针灸医院,山西 太原 030006

自发性高血压 脑白质损伤 腧穴降压组方 室旁核炎症损伤 JNK-MCP1通路

2024

山西中医药大学学报

山西中医药大学学报

ISSN:
年,卷(期):2024.25(9)