基于钟基因Clock和Bmal1调控探究辰时针刺自发性高血压大鼠的降压机制
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国家重点研发计划“中医药现代化研究”重点专项计划(2018YFC1707803);河北省中医药管理局项目(2017054);河北省财政厅项目(361025)


Antihypertensive Mechanism of Acupuncture During the Period of the Day from 7 a.m. to 9 a.m. in Spontaneously Hypertensive Rats Based on the Regulation of Circadian Clock Genes Clock and Bmal1
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    摘要:

    目的 以自发性高血压大鼠(spontaneous hypertensive rat,SHR)为观察对象,探究针刺降压的钟基因调控作用。方法 将24只SHR随机分为针刺组和模型组,12只Wistar-Kyoto(WKY)大鼠作为正常组。针刺组选择辰时针刺SHR双侧曲池、足三里穴,模型组和正常组仅接受与针刺组同等强度的捆绑操作。4周后,各组分别在辰、酉时随机抽取6只大鼠,测量鼠尾收缩压(systolic blood pressure, SBP)和舒张压(diastolic blood pressure, DBP),然后检测血清5-羟色胺(5-hydroxytryptamine,5-HT)、褪黑素(melatonin, MT)的含量以及心脏生物钟基因Clock和Bmal1的表达水平。结果 分组因素对SBP、DBP、血清MT含量、Clock表达结果的RQ值、Bmal1表达结果的RQ值的主效应均有统计学意义(P<0.05),时辰因素对各指标的主效应和两者的交互作用均无统计学意义(P>0.05)。模型组辰、酉两个时辰的SBP和DBP均高于正常组(P<0.05),针刺组辰时的SBP和DBP及酉时的SBP均低于模型组(P<0.05)。模型组辰时MT含量较正常组降低,5-HT含量较正常组升高(P<0.05),针刺组辰时MT含量较模型组升高,5-HT含量较模型组降低(P<0.05);针刺组酉时的MT含量较模型组升高(P<0.05)。针刺组辰时心脏Clock基因表达水平和酉时心脏Bmal1基因表达水平较模型组升高(P<0.05)。结论 辰时针刺可以降低SHR的“双峰”血压,其作用机制可能与提高血清MT含量,减少5-HT含量以及提高心脏Clock和Bmal1基因的表达水平有关。

    Abstract:

    Objective To investigate the regulatory effect of circadian clock genes in reducing blood pressure by acupuncture in spontaneously hypertensive rats (SHRs). Methods A total of 24 SHRs were randomly divided into acupuncture group and model group, and 12 Wistar Kyoto (WKY) rats were selected as normal group. The rats in the acupuncture group were given acupuncture at bilateral Quchi and Zusanli acupoints during the period of the day from 7 a.m. to 9 a.m., and those in the model group and the normal group were tied up with the same intensity as the acupuncture group. Four weeks later, six rats were randomly selected from each group during the periods of the day from 7 a.m. to 9 a.m. and from 5 p.m. to 7 p.m. to measure rat tail systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as the serum levels of 5-hydroxytryptamine (5-HT) and melatonin (MT) and the mRNA expression of the circadian clock genes Clock and Bmal1. Results The main effects of grouping factors on SBP, DBP, serum MT, and RQ values of the expression of Clock and Bmal1 were statistically significant (P<0.05), while the main effect of time factor on each index and the interaction between them was not statistically significant (P>0.05). Compared with the normal group, the model group had significantly higher SBP and DBP during the periods of the day from 7 a.m. to 9 a.m. and from 5 p.m. to 7 p.m. (P<0.05), and compared with the model group, the acupuncture group had significantly lower SBP and DBP during the period of the day from 7 a.m. to 9 a.m. and a significantly lower SBP during the period of the day from 5 p.m. to 7 p.m. (P<0.05). Compared with the normal group, the model group had a significant reduction in MT and a significant increase in 5-HT during the period of the day from 7 a.m. to 9 a.m. (P<0.05); compared with the model group, the acupuncture group had a significant increase in MT and a significant reduction in 5-HT during the period of the day from 7 a.m. to 9 a.m. (P<0.05), as well as a significant increase in MT during the period of the day from 5 p.m. to 7 p.m. (P<0.05). Compared with the model group, the acupuncture group had a significant increase in the mRNA expression of Clock during the period of the day from 7 a.m. to 9 a.m. and a significant increase in the mRNA expression of Bmal1 during the period of the day from 5 p.m. to 7 p.m. (P<0.05). Conclusion Acupuncture during the period of the day from 7 a.m. to 9 a.m. can reduce "bimodal" blood pressure of SHR, possibly by increasing serum MT, reducing 5-HT, and increasing the mRNA expression of the Clock and Bmal1 genes in the heart.

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王艳君,李宏坤,孙明新,李艳红,薛维华.基于钟基因Clock和Bmal1调控探究辰时针刺自发性高血压大鼠的降压机制[J].安徽中医药大学学报,2020,39(5):72-77

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  • 在线发布日期: 2020-10-15