石决牡蛎汤通过p38MAPK通路改善自发性高血压大鼠血管重构的机制研究

Mechanism Study of Shijue Muli Decoction in Improving Vascular Remodeling of Spontaneously Hypertensive Rat Through p38MAPK Signaling Pathway

【目的】探讨石决牡蛎汤通过p38丝裂原活化蛋白激酶(p38MAPK)信号通路改善自发性高血压大鼠(SHR)血管重构的作用。【方法】将40只16周龄自发性高血压大鼠随机分为模型对照组,石决牡蛎汤高、中、低剂量组,卡托普利组,每组8只;将8只Wistar-Kyoto大鼠设为正常对照组。治疗8周后,采用苏木精—伊红(HE)染色法观察胸主动脉形态,光镜下采用计算机图像分析系统测量血管内膜中层厚度(IMT)、管腔直径(LD),酶联免疫吸附法(ELISA)测定血清中内皮素-1(ET-1)水平,硝酸还原酶法测定血清中一氧化氮(NO)水平,免疫组织化学法检测磷酸化p38MAPK(p-p38MAPK)在胸主动脉组织中的表达水平。【结果】与模型对照组比较,石决牡蛎汤中、高剂量组及卡托普利组收缩压和舒张压、ET-1水平均显著降低,NO水平增高,中药高剂量组及卡托普利组IMT、IMT/LD值显著降低,差异均有统计学意义(P<0.05)。免疫组织化学结果显示,石决牡蛎汤中、高剂量组及卡托普利组能较显著抑制p-p38MAPK在胸主动脉的表达。【结论】石决牡蛎汤可能通过抑制p38MAPK信号通路、调节ET/NO系统改善自发性高血压大鼠血管重构。

Objective To explore the effect of Shijue Muli Decoction （SMD） on improving vascular remodeling of spontaneously hypertensive rats（SHRs） by p38MAPK signaling pathway. Methods Forty 16-week old SHRs were randomly divided into model control group, high-, middle- and low-dose SMD groups, and Captopril group, 8 rats in each group. In addition, 8 Wistar-Kyoto rats were used as the blank control group. After 8-week medication, pathological features of thoracic aorta were observed by HE staining, intima-media thickness （IMT） and lumen diameter （LD） were measured by computer image analysis system, serum endothelin （ET-1） level was detected by enzyme-linked immunosorbent assay（ELISA）, serum nitric oxide（NO） level was detected by nitrate reductase method, and the expression of phosphorylated-p38MAPK （p-p38MAPK） in the thoracic aorta was determined by immunohistochemistry. Results Compared with the model control group, the values of systolic blood pressure and diastolic blood pressure as well as ET-1 level were lower and NO level was higher in high- and middle-dose SMD groups and Captopril group, and IMT and IMT/LD were markedly decreased in high-dose group and Captopril group （P 〈 0.05）. The immunohistochemical results showed that the expression levels of p-p38MAPK in the thoracic aorta were inhibited in high- and middle-dose groups and Captopril group. Conclusion SMD can improve vascular remodeling of SHRs through inhibiting p38MAPK signaling pathway and ET/NO system.