中文摘要：

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。

英文摘要：

Objective To investigate the effect of interleukin-22（IL-22） on the phosphorylation of threonine 495（thr495） in human umbilical vein endothelial cells （HUVECs） and endothelial function and blood pressure in mice via the signal transduction and transcriptional activation of factor 3（Stat3） pathway,aiming at providing new thought for the treatment of hypertension .Methods HUVECs were randomly divided into 6 groups,and each was treated with dimethyl sulfoxide ,recombinant human IL-22,S31-201,S31-201 ＋IL-22,Go6976,or Go6976＋IL-22,then the activation of Stat3 pathway and phosphorylation of the inhibitory locus thr 495 of nitric oxide synthase（eNOS） were measured.A total of 32 C57bl/6 mice were randomly divided into 4 group.The first group were treated with phosphate buffer saline （ control group ） , the second group were treated with IL-22 （ model group ） , the third group were treated with IL-22 ＋dimethyl sulfoxide （S31-201 control group）,and the fourth group were treated with IL-22＋S31-201（S31-201 model group）.After 14 days treatment,systolic blood pressure（SBP）,NO production,activation of Stat3,and the phosphorylation of eNOS thr 495 were measured.Results The phosphorylation of thr495 and the activation of Stat3 were increased in HUVECs treated with recombinant human IL-22.The induced effect could be prevented by Stat3 inhibitor S31-201,but not by the protein kinase C inhibitor Go6976.The rise of SBP,the increased activation of aorta Stat3 and the phosphorylation of eNOS thr495,the decrease of NO expression in model group were observed , whereas the effect above-mentioned could be prevented by S31-201.Conclusion IL-22 could mediate endothelial dysfunction and hypertension by activating Stat 3 pathway.It might be may be a novel therapy of prevention and treatment of hypertension to inhibit the produce of IL-22 or the activation of Stat3 pathway.