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4-羟基-苯丙噁唑-2-酮对非酒精性脂肪肝病模型大鼠炎症和凋亡信号通路的影响
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| 篇名： | 4-羟基-苯丙噁唑-2-酮对非酒精性脂肪肝病模型大鼠炎症和凋亡信号通路的影响 |
| TITLE： | Effects of 4-hydroxy-2（3H）-benzoxazolone on Inflammatory and Apoptosis Signaling Pathways in Non-alcoholic Fatty Liver Disease Model Rats |
| 摘要： | 目的：探讨4-羟基-苯丙噁唑-2-酮对非酒精性脂肪肝病（NAFLD）模型大鼠炎症和凋亡信号通路的影响。方法：将SD大鼠分为正常对照组（10只）和造模组（50只），正常对照组大鼠给予基础饲料，造模组大鼠给予高脂饲料以复制NAFLD模型。造模成功后，将大鼠分为正常对照组、模型组、水飞蓟宾组（26.25mg/kg）和4-羟基-苯丙噁唑-2-酮高、中、低剂量组（100、50、25mg/kg），每组8只，正常对照组和模型组大鼠灌胃0.6％羧甲基纤维素钠溶液，其余各组大鼠灌胃相应药物，灌胃体积为10mL/kg，每天1次，连续4周。末次给药后，检测大鼠血清中白蛋白（ALB）、总蛋白（TP）、球蛋白（GLB）水平，ALB/GLB比值以及游离脂肪酸（FFA）水平；采用TUNEL染色法观察大鼠肝细胞凋亡情况；采用Westernblot法检测大鼠肝组织中炎症信号通路相关蛋白[Toll样受体4（TLR4）、髓样分化因子88（MyD88）、核因子κBp65（NF-κBp65）、NF-κB抑制蛋白（IκBα）]的表达水平或磷酸化水平以及凋亡信号通路相关蛋白[B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、胱天蛋白酶3（caspase-3）]的表达水平。结果：与模型组比较，4-羟基-苯丙噁唑-2-酮各剂量组大鼠血清中TP（低剂量组除外）、GLB、FFA水平和肝组织中TLR4（低剂量组除外）、MyD88（中剂量组除外）、caspase-3蛋白表达水平以及NF-κBp65、IκBα的磷酸化水平均显著降低（P＜0.05或P＜0.01），血清中ALB/GLB比值和肝组织中Bcl-2/Bax比值均显著升高（P＜0.05或P＜0.01），肝细胞凋亡现象有所改善。结论：4-羟基-苯丙噁唑-2-酮可改善大鼠NAFLD状态，其作用机制可能与抑制肝组织中TLR4/MyD88/NF-κB信号通路相关蛋白和凋亡相关蛋白表达有关。 |
| ABSTRACT： | OBJECTIVE：To inv estigate the effects of 4-hydroxy-2（3H）-benzoxazolone on inflammatory and apoptosis signaling pathways in non-alcoholic fatty liver disease （NAFLD）model rats. METHODS ：SD rats were divided into normal control group（10 rats）and modeling group （50 rats）. Normal control group was given basic diet ，and modeling group were given high-fat diet to induce NAFLD model. After modeling ，the rats were divided into normal control group ，model group ，silibinin group （26.25 mg/kg），and 4-hydroxy-2（3H）-benzoxazolone high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 8 rats in each group. Normal control group and modeling group were given 0.6％ CMC-Na intragastrically ，and other groups were given relevant medicine 10 mL/kg intragastrically ，once a day ，for consecutive 4 weeks. After last medication ，the serum levels of albumin（ALB），total protein （TP），globulin（GLB），ALB/GLB and free fatty acid （FFA）were detected ；TUNEL staining was used to observe the apoptosis of rat hepatocytes. Western blot assay was used to detect the protein expression and phosphorylation level of inflammatory signaling pathway related proteins [Toll-like receptor 4（TLR4），myeloid differentiation factor 88（MyD88）， nuclear factor-κB p65（NF-κB p65），NF-κB inhibitor protein（IκBα）] in liver tissue as well as the expression of apoptosis signaling pathway related proteins [B cell lymphoma 2（Bcl-2），Bax，caspase-3]. RESULTS ：Compared with model group ，serum levels of TP （except for low-dose group ），GLB and FFA ，the protein expression of TLR 4（except for low-dose group ），MyD88 （except for medium-dose group ）and caspase- 3，the phosphorylation levels of NF-κB p65 and IκBα protein were decreased significantly（P＜0.05 or P＜0.01）. The ratio of A LB/GLB in serum and the ratio of Bcl- 2/Bax in liver tissue were significantly increased（P＜0.05 or P＜0.01），and the phenomenon of hepatocyte apoptosis was improved. CONCLUSIONS ：4-hydroxy-2 （3H）-benzoxazolone can ameliorate NAFLD in rats ，and the mechanism may be associated with inhibiting the expression TLR 4/ MyD88/NF-κB signaling pathway-related proteins and apoptosis-related proteins in liver tissues. |
| 期刊： | 2021年第32卷第11期 |
| 作者： | 徐万鹏，林军，梁英琴，周焕芳，张华，黄仕珍，孙雪梅，韦秀桂，王红园，刘林 |
| AUTHORS： | XU Wanpeng，LIN Jun，LIANG Yingqin， ZHOU Huanfang，ZHANG Hua，HUANG Shizhen，SUN Xuemei，WEI Xiugui，WANG Hongyuan，LIU Lin |
| 关键字： | 4-羟基-苯丙噁唑-2-酮；非酒精性脂肪肝病；炎症；凋亡；TLR4/MyD88/NF-κB信号通路；大鼠 |
| KEYWORDS： | 4-hydroxy-2（3H）-benzoxazolone；Non-alcoholic fatty liver disease ；Inflammation；Apoptosis；TLR4/MyD88/NF- |
| 阅读数： | 195 次 |
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