薄荷醇介导的TRPM8激活促进寒冷应激创伤小鼠创面愈合  

Menthol mediated activation of TRPM8 promotes wound healing in cold-stressed mice

作　　者：于浩 杨昕 李钰婕 孔媛 高伟 童慧昕 梁琳琅 YU Hao;YANG Xin;LI Yu-jie;KONG Yuan;GAO Wei;TONG Hui-xin;LIANG Lin-lang(Department of Endocrinology,Northern Theater Command General Hospital,Shenyang 110016,China)

机构地区：[1]北部战区总医院内分泌科,辽宁沈阳110016

出　　处：《解剖科学进展》2024年第4期409-412,共4页Progress of Anatomical Sciences

基　　金：辽宁省科学技术基金面上项目(2022-MS-048)。

摘　　要：目的探究薄荷醇介导的TRPM8激活对寒冷应激创伤小鼠创面愈合的改善作用及机制。方法野生型小鼠随机分为WT组和WT+Menthol组,每组5只。TRPM8-/-小鼠随机分为TRPM8-/-组和TRPM8-/-+Menthol组,每组5只。各组小鼠建立寒冷应激创伤模型后,给予相应饲料喂养28 d后,收集血清、创面皮肤组织和棕色脂肪组织进行检测。HE染色观察小鼠创面皮肤组织病理损伤情况;ELISA法检测小鼠血清中氧化应激因子MDA、CRP和SOD以及炎症因子TNF-α和IL-1β水平;免疫荧光检测小鼠棕色脂肪组织中钙离子和mtROS水平;Western blot检测小鼠棕色脂肪组织中TRPM8和UCP1蛋白表达水平。结果给予薄荷醇改善寒冷应激创伤的野生型小鼠创面病理损伤,降低小鼠血清中MDA、CRP、TNF-α和IL-1β水平并增加SOD水平;增加小鼠棕色脂肪组织中钙离子和mtROS水平,上调棕色脂肪组织中TRPM8和UCP1蛋白表达。给予薄荷醇对TRPM8敲除小鼠创面病理损伤、血清中MDA、CRP、SOD、TNF-α和IL-1β水平、棕色脂肪组织中钙离子和mtROS水平以及TRPM8和UCP1蛋白表达水平无明显影响。结论薄荷醇促进寒冷应激创伤的创面愈合并改善氧化应激和炎症,其机制可能与激活棕色脂肪细胞TRPM8通道导致钙离子内流,诱导mtROS介导的UCP1激活并促进非寒颤性产热有关。Objective To explore the effect and mechanism of menthol-mediated TRPM8 activation on wound healing in cold-stressed mice.Methods Wild-type mice were randomly divided into WT group and WT+Menthol group with 5 mice in each group.TRPM8~(-/-)mice were randomly divided into TRPM8~(-/-)group and Trpm8~(-/-)+Mentol group,with 5 mice in each group.Mice in each group were given corresponding feed for 28 days after establishing cold stress trauma model,and serum,wound skin tissue and brown adipose tissue were collected for detection.HE staining was used to observe the pathological damage of skin tissue in mice.ELISA was used to detect the levels of oxidative stress factors MDA,CRP and SOD,inflammatory factors TNF-αand IL-1βin serum of mice.Immunofluorescence was used to detect the levels of calcium ion and mtROS in brown adipose tissue of mice.Western blot was used to detect the expression levels of TRPM8 and UCP1 proteins in brown adipose tissue of mice.Results Menthol could improve the pathological injury of wild-type mice with cold stress trauma,reduce the levels of MDA,CRP,TNF-αand IL-1βin serum and increase the level of SOD,increase the level of calcium ion and mtROS in brown adipose tissue of mice,and up-regulate the expressions of TRPM8 and UCP1 proteins in brown adipose tissue.Menthol administration had no significant effect on the pathological injury,the levels of MDA,CRP,SOD,TNF-αand IL-1βin serum,the levels of calcium ion and mtROS in brown adipose tissue,and the expression levels of TRPM8 and UCP1 proteins of TRPM8 knockout mice.Conclusion Menthol promotes wound healing of cold stress trauma and improves oxidative stress and inflammation,and its mechanism may be related to activating TRPM8 channel of brown adipocytes,leading to calcium influx,inducing activation of UCP1 mediated by mtROS and promoting non-shivering thermogenesis.

关 键 词：薄荷醇 寒冷应激创伤 创面愈合 TRPM8 棕色脂肪 UCP1 

分 类 号：R645[医药卫生—外科学]