BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regen...BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province,No.LQ20H310002the Scientific Technology Projects of Health and Medicine of Zhejiang Province,No.2020KY308and the Huzhou Science and Technology Fund,No.2020GY39.
文摘BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy(PHx).At present,there is a lack of recognized safe,effective,and stable drugs to promote liver regeneration.It has been reported that vagus nerve signaling is beneficial to liver regeneration,but the potential mechanism at play here is not fully understood.AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.METHODS A PHx plus hepatic vagotomy(Hv)mouse model was established.The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice.In order to further investigate the role of interleukin(IL)-22 in liver regeneration inhibition mediated by Hv,the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured.The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.RESULTS Compared to control-group mice,Hv mice showed severe liver injury and weakened liver regeneration after PHx.Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3(STAT3)pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx.Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury,while treatment with IL-22 binding protein(an inhibitor of IL-22 signaling)reduce the concentration of IL-22 induced by PHx,inhibits the activation of the STAT3 signaling pathway in the liver after PHx,thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.CONCLUSION Hv attenuates liver regeneration after hepatectomy,and the mechanism may be related to the fact that Hv downregulates the production of IL-22,then blocks activation of the STAT3 pathway.
文摘目的研究原发性IgA肾病患者血清中白细胞介素-22(interleukin-22,IL-22)及血细胞相关参数包括系统性免疫炎症指数(systemic immune inflammatory index,SII)、血小板与淋巴细胞比值(platelet to lymphocyte ratio,PLR)、中性粒细胞与淋巴细胞比值(monocyte to lymphocyte ratio,NLR)等炎症指标表达水平变化,探讨其与疾病进展危险因素的关系。方法收集徐州医科大学附属医院经肾活检确诊的60例原发性IgA肾病和40例健康对照的临床资料,采用ELISA法检测血清中IL-22水平,进行独立样本t检验、Spearman相关性分析、ROC曲线、二元Logistic回归分析,研究IL-22水平及SII、PLR、NLR等指标评估IgA肾病疾病进展的作用。结果和健康对照相比,IgA肾病患者血清IL-22、SII、PLR、NLR水平显著升高,Spearman相关性分析表明IL-22水平与SII(r=0.342,P=0.001)、WBC(r=0.226,P=0.025)、NLR(r=0.371,P=0.000)呈正相关,和eGFR(r=-0.296,P=0.003)呈负相关。进一步进行ROC曲线分析,结果显示IL-22的曲线下面积最大(0.882),其次分别为SII(0.766)、NLR(0.727)和PLR(0.693)。二元Logistic回归分析表明血清中IL-22水平是IgA肾病的独立危险因素。结论IL-22是IgA肾病患者疾病进展的独立影响因素,早期或可以通过检测IL-22水平评估IgA肾病病情进展。
