论文部分内容阅读
目的:探讨高血压神经-内分泌-免疫调节的内在机制和滋阴潜阳方作用的可能环节。方法:SD大鼠120只,复制二肾一夹高血压大鼠模型(2K1C-RHR),假手术组大鼠右肾动脉只分离不狭窄;取模型成功大鼠分为模型组、滋阴潜阳方高、中、低剂量组(32,16,8g·kg-1)、氯沙坦钾组(0.005g·kg-1)及天麻钩藤颗粒组(1.5g·kg-1),连续ig给药4周。采用无创血压测量仪观察其对血压的影响,放射性免疫法检测血浆血管紧张素Ⅱ(AngⅡ)含量变化,Westernbloting法测定各组大鼠外周血淋巴细胞血管紧张素1型受体(AT1R)和兔抗磷酸化蛋白激酶C(p-PKC)的表达水平变化,ELISA法测定各组大鼠外周血淋巴细胞内三磷酸肌醇(IP3),二酰甘油(DAG)以及血清中白细胞介素-4(IL-4),白细胞介素-6(IL-6)含量变化。结果:与假手术组比较,模型组大鼠血压明显升高,大鼠血浆AngⅡ水平明显升高,大鼠外周血淋巴细胞AT1R,p-PKC蛋白的表达明显升高,外周血淋巴细胞内IP3,DAG含量明显升高,血清中IL-4,IL-6的含量明显升高,均具有统计学差异(P<0.05,P<0.01);与模型组比较,滋阴潜阳方高、中、低剂量组均能显著降低模型大鼠血压水平(P<0.01),滋阴潜阳方中、低剂量组能够降低大鼠血浆AngⅡ水平(P<0.05),高剂量组能够降低肾性高血压大鼠外周血淋巴细胞AT1R,p-PKC蛋白的表达水平(P<0.01,P<0.05),同时高剂量组能够明显降低外周血淋巴细胞内IP3,DAG(P<0.01,P<0.01)以及血清中IL-4,IL-6的含量(P<0.05,P<0.01)。结论:肾性高血压病的发病机制可能与外周血淋巴细胞AT1R的过度表达,以及胞内磷脂酰肌醇信号通路的激活有关;滋阴潜阳方可以从多环节抑制信号通路的激活,对高血压的神经、内分泌、免疫功能发挥整体调节作用。
Objective: To explore the underlying mechanism of hypertension-neuroendocrine-immune regulation and the possible link of action of Ziyin-Qianyang prescription. Methods: 120 SD rats were used to duplicate 2K1C-RHR model. Rats in sham-operation group were only separated and not stenosed. Rats in model group were divided into model group, Yanggan high, medium and low dose groups (32,16,8 g · kg-1), losartan potassium group (0.005g · kg-1) and Tianma Gouteng granules group (1.5g · kg-1) ig administration for 4 weeks. The blood pressure was measured with a noninvasive blood pressure meter. The contents of plasma angiotensin Ⅱ (AngⅡ) were measured by radioimmunoassay. The expressions of angiotensin Ⅱ type 1 receptor (AT1R) and peripheral blood lymphocytes were detected by Western blotting. The levels of p-PKC and p-PKC in peripheral blood were measured by ELISA. The levels of inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) and interleukin-4 (IL-4), interleukin-6 (IL-6) content changes. Results: Compared with the sham-operation group, the blood pressure of the model group was significantly increased and the level of AngⅡ in the model group was significantly increased. The expression of AT1R and p-PKC protein in the peripheral blood lymphocytes was significantly increased in the model group. The expression of IP3 , DAG content increased significantly, serum IL-4, IL-6 levels were significantly increased, both with statistical significance (P <0.05, P <0.01); compared with the model group, (P <0.01). The middle and low doses of Ziyinqianyang could decrease the level of AngⅡ in rats (P <0.05), and the high dose of Ziyinqianyang can reduce the levels of renal high The levels of AT1R and p-PKC protein in peripheral blood lymphocytes were significantly decreased in high blood pressure group (P <0.01, P <0.05) Serum levels of IL-4 and IL-6 (P <0.05, P <0.01). Conclusion: The pathogenesis of renal hypertension may be related to the overexpression of AT1R in peripheral blood lymphocytes and the activation of intracellular phosphatidylinositol signaling pathway. Ziyinqianyang can inhibit the activation of signaling pathway from multiple aspects Hypertensive nerves, endocrine, immune function play an overall regulatory role.