虚燥更平散对更年期高血压大鼠血压及血压变异性影响的研究

Effect of Xu-zao-geng-ping-granule on Blood Pressure Variability of the Rats with Menopausal Hypertension

目的运用虚燥更平散干预更年期高血压大鼠,观察大鼠血压、血压变异性(BPV)及其神经递质指标〔血清儿茶酚胺(CA)、神经肽Y(NPY)、神经降压素(NT)〕和内分泌指标〔血清雌二醇(E2)、促卵泡生成激素(FSH)、促黄体生成激素(LH)〕水平的变化,探讨虚燥更平散对更年期高血压大鼠血压、BPV的影响及其可能的机制。方法运用摘除自发性高血压大鼠(SHR大鼠)卵巢的方法建立更年期高血压大鼠复合实验动物模型,对造模大鼠行阴道脱落细胞学检查及血清性激素〔E2、FSH、LH、睾酮(T)、孕酮(P)〕水平测定,进行造模评价。将48只SHR大鼠按随机数字表法随机分为6组:更年期高血压中药组(6只)、更年期高血压西药组(6只)、更年期高血压空白对照组(空白对照组,12只)、假手术组(12只)、SHR组(12只),另设Wistar组为正常对照组(6只)。更年期高血压中药组大鼠灌服虚燥更平散,更年期高血压西药组灌服缬沙坦,其余各组均灌服等体积的0.9%氯化钠溶液。观察各组大鼠血压、BPV的变化,比较血清CA、NPY、NT和血清E2、FSH、LH的水平。结果 (1)更年期高血压大鼠复合实验动物模型造模评价:去势大鼠已无原有动情周期生理性变化,去势彻底,符合更年期特征。与假手术组、SHR组比较,空白对照组大鼠血清E2、T、P水平明显下调,FSH、LH水平明显上调,差异有统计学意义(P<0.05);SHR组、空白对照组大鼠手术前后血压值差异无统计学意义(P>0.05)。(2)血压:各组治疗后5～60 d同一时间点血压值对比,差异有统计学意义(P<0.05)。(3)血压变异性:与空白对照组比较,更年期高血压中药组、更年期高血压西药组BPV明显降低,差异有统计学意义(P<0.05)。(4)神经递质指标:与空白对照组比较,更年期高血压中药组及更年期高血压西药组的CA、NPY、NT水平上调,差异有统计学意义(P<0.05)。(5)内分泌指标:与空白对照组比较,更年期高血压中药组E2水平下调,FSH、LH水平上调,差异有统计学意义(P<0.05)。结论 (1)运用摘除SHR大鼠卵巢的方法可建立符合更年期高血压的实验动物模型。(2)虚燥更平散能降低更年期高血压大鼠的血压,调节更年期高血压大鼠的BPV。(3)虚燥更平散可以改善更年期高血压大鼠内环境,调节神经递质及内分泌指标,可能是有效治疗更年期高血压的机制。

Objective To evaluate the effects of Xu - zao - geng - ping - granule on menopausal hypertensive （MP） rats regarding blood pressure （BP）, blood pressure variability （BPV）, catecholamine （CA）, neuropeptide Y （NPY）, neuro- tensin （NT）, estradiol （E2 ）, follicle stimulating hormone （FSH）, and luteinizing hormone （LH）, so as to discuss the effects of the medicine on reducing BP and BPV and its mechanism in MP rats. Methods MP rat model was established by removing the ovaries from spontaneously hypertensive rats （SHR）. Vaginal smear and serum sex hormone （E2, FSH, LH, testosterone, and progesterone） tests were conducted. A total of 48 rats were divided using random number table into a MP TCM group （6）, a MP western medicine group （6）, a MP control group （12）, a fake surgery group （12）, and a SHR group （12）. Six Wistar rats were assigned as the normal control group. Rats in menopausal hypertensive TCM group were administered with xu - zao- geng- ping- granule, rats in menopausal hypertensive western medicine group were administered with valsartan, while rats in other groups were administered with normal saline solution of the same volume. Changes of BP, BPV and levels of CA, NPY, NT, E2, FSH, LH were observed and compared between groups. Results The rats removed of ovaries did not show physiologi- cal changes with estrous cycles, which was consistent with menopausal characteristics. The rats in the MP control group had sig- nificantly decreased levels of serum E2 , testosterone, and progesterone, and significantly increased levels of FSH and LH than the fake surgery and SHR groups （P 〈 0. 05）. No significant changes of BP was observed in rats of the MP control group com- pared with the fake surgery and SHR groups （P 〉 0. 05 ）. BP of rats in different groups were significantly different at the same time points between day 5 and day 60 （ P 〈 0. 05 ）. BPV of the TCM group and western medicine group were significantly lower than that of the MP control group （P 〈0. 05 ）. Levels of CA, NYP, and NT of TCM group and western medicine group were significantly higher than that of the menopause hypertension control group （ P 〈 0. 05 ）. TCM group had significantly lower level of E2, and higher levels of FSH and LH than the MP control group （ P 〈 0.05）. Conclusion Menopausal hypertensive rat model can be established through removal of the rats＇ ovaries. Xu - zao - geng - ping - granule may reduce the blood pressure and regulate the BPV, transmitter and endocrine indices of menopausal hypertensive rats. This medicine might be an effective therapy to treat menopausal hypertension.