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-
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