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目的探讨白细胞介素22(IL-22)经信号转导和转录激活因子3(Stat3)通路对人脐静脉内皮细胞苏氨酸495(thr495)磷酸化及小鼠内皮功能和血压的影响,为治疗高血压提供新的思路。方法随机将人脐静脉内皮细胞(HUVECs)分成6组,分别为二甲基亚砜溶剂处理组(对照组),重组人IL-22组,S31-201组,S31-201+IL-22组,Go6976组,Go6976+IL-22组,各组经相应处理后检测Stat3通路活化状态和一氧化氮合酶(e NOS)抑制性位点thr495磷酸化的表达。32只C57BL/6小鼠随机分成4组,均经腹腔注射给药,第一组给予磷酸盐缓冲液(PBS)(对照组),第二组给予15μg/kg IL-22(模型组),第三组给予15μg/kg IL-22+二甲基亚砜溶剂(S31-201对照组),第四组给予15μg/kg IL-22+5 mg/kg S31-201(S31-201模型组)。处理14 d后测量尾动脉收缩压、主动脉NO表达、Stat3通路活化状态和thr495磷酸化的表达。结果 HUVECs经过重组人IL-22处理后可以引起Stat3通路活化及e NOS thr495磷酸化增多,这种作用可以被Stat3通路阻断剂S31-201阻断(P<0.05),但蛋白激酶C(PKC)阻断剂Go6976对其没有影响(P>0.05)。IL-22组小鼠较对照组收缩压显著升高,主动脉Stat3通路活化及e NOS thr495磷酸化增多,NO的表达下降,这些作用均可被S31-201阻断(均P<0.05)。结论 IL-22可以通过激活Stat3通路引起内皮功能障碍和高血压。抑制IL-22的生成或Stat3通路的激活是一个预防或治疗高血压的方法。
Objective To investigate the effects of interleukin-22 (IL-22) on the phosphorylation of threonine 495 (thr495) and endothelial function and blood pressure in human umbilical vein endothelial cells by the signal transducers and activators of transcription 3 (Stat3) pathway. Treatment of high blood pressure provides new ideas. Methods Human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: dimethylsulfoxide solvent treatment group (control group), recombinant human IL-22 group, S31-201 group, S31-201 + IL-22 group , Go6976 group and Go6976 + IL-22 group. The expressions of Stat3 pathway activation and phosphorylation of thr495, an inhibitor of nitric oxide synthase (e NOS), were detected in all the groups. Thirty-two C57BL / 6 mice were randomly divided into four groups, all of which were injected intraperitoneally. The first group was given phosphate buffered saline (PBS) (control group), the second group was given 15μg / kg IL-22 The third group was given 15μg / kg IL-22 + dimethyl sulfoxide solvent (S31-201 control group), the fourth group was given 15μg / kg IL-22 + 5 mg / kg S31-201 (S31-201 model group) . The tail artery systolic pressure, aortic NO expression, Stat3 pathway activation status and thr495 phosphorylation were measured after 14 days of treatment. Results After HUVECs were treated with recombinant human IL-22, the activation of Stat3 pathway and phosphorylation of eNOS thr495 were induced by HUVECs. This effect was blocked by Stat3 pathway inhibitor S31-201 (P <0.05), but protein kinase C (PKC ) Blocker Go6976 had no effect (P> 0.05). The systolic blood pressure of IL-22 group was significantly higher than that of control group. The activation of Stat3 pathway in the aorta and the increase of phosphorylation of eNOS thr495 and the decrease of NO expression were all inhibited by S31-201 (all P <0.05). Conclusion IL-22 can cause endothelial dysfunction and hypertension by activating Stat3 pathway. Inhibition of IL-22 production or activation of the Stat3 pathway is a method of preventing or treating hypertension.