【摘要】 目的 基于网络药理学探索化痰祛瘀方对自发性高血压大鼠早期肾损害保护的作用机制。方法 采用网络药理学的理论框架，中药活性成分筛选、潜在靶点预测、通络富集分析等方法对化痰祛瘀方治疗高血压早期肾损害的作用机制进行分析。试验验证：50只自发性高血压大鼠(SHR)随机分为，模型组、化痰祛瘀方组、氯沙坦钾组、中西医结合组、化痰祛瘀方+NOS抑制剂组，另外取10只正常血压大鼠(Wistar-kyoto, WKY)作为对照组，灌胃治疗4周，观察各组早期肾损害相关指标及肾组织一氧化氮合成的限速酶(NOS)及NO的变化。结果 (1)化痰祛瘀方中8味中药具有较好ADME性质的潜在主要活性成分共100个，其中86个活性成分及对应的58个靶点与高血压肾损害关系密切，可能通过cGMP-PKG信号通络、PI3K-Ak信号通络、MAPK信号通络、VEGF信号通络、NF-kappa B信号通络、Renin-angiotensin系统等途径治疗高血压肾损害。(2)化痰祛瘀方组、氯沙坦钾组及中西医结合组均能减轻SHR的早期肾损害，但中西医结合组更加明显(P<0.05),其余各组作用不明显(P>0.05)。(3)氯沙坦钾组及中西医结合组能升高SHR肾组织NO浓度及增强NOS活性(P<0.05),但氯沙坦钾组及化痰祛瘀方+NOS抑制剂组无此作用(P>0.05)。结论 化痰祛瘀方通过保护血管内皮功能以改善SHR的早期肾损害。更多还原

【Abstract】 Objective To reveal the mechanism of Huatan Quyu Formula against early renal damage in spontaneously hypertensive rats(SHRs).Methods With the methods of network pharmacology, active components of Chinese medicinals in Huatan Quyu Formula were screened out and potential targets of the components were predicted.Moreover, the related pathways were analyzed, thereby clarifying the mechanism.As for the experimental verification, 50 SHRs were randomized into model group, Huatan Quyu Formula group(H group),losartan potassium group(L group),Huatan Quyu Formula+losartan potassium group(HL group),and Huatan Quyu Formula+L-NAME group(Ni group),and another 10 WKY rats were used as the control.After 4 weeks of treatment with respective drugs(ig),the indexes of early renal damage and the variation of nitric oxide synthase(NOS)and nitric oxide(NO)in kidney were observed.Results(1)A total of 8 medicinals in the formula showed excellent ADME and 100 potential active components of them were screened out.Among them, 86 active components and the corresponding 58 targets were closely related to the hypertensive renal damage.The targets were mainly involved in the cGMP-PKG signaling pathway, PI3 K-Ak signaling pathway, MAPK signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, and Renin-angiotensin system.(2)H group, L group, and HL group all showed relief of the early renal damage in SHR,particularly the HL group(P< 0.05).Other groups had no obvious changes(P>0.05).(3)H group and HL group demonstrated increase in nitric oxide(NO)level and nitric oxide synthase(NOS)activity in the kidney, while L group and Ni group had no similar phenomena(P>0.05).Conclusion Huatan Quyu Formula alleviates early renal damage in SHRs by protecting endothelium function.更多还原