rhIL-1RA对MCD饮食诱导NASH小鼠炎症的干预作用及机制的研究
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摘要
目的探讨rhIL-1RA对MCD饮食诱导NASH小鼠炎症的作用及其作用机制。方法将90只5周龄的SPF级小鼠随机分为3组,即正常对照组、模型组、干预组,每组30只,先给予普通SPF级饲料适应性喂养1周;使用MCS饲料喂养正常对照组小鼠,而使用MCD饲料喂养模型组、干预组小鼠,所有小鼠每日常规给予正常饮水。模型组小鼠每日予1 mL生理盐水腹腔注射,干预组小鼠每日予人重组白介素-1受体拮抗剂20mg/kg腹腔注射,连续喂养4周后处死。检测小鼠的体重、肝重、肝功能及血脂,肝组织行HE染色,观察其病理学上的变化。结果实验结束后,模型组与正常组相比体重、肝重减少,HE染色发现其脂肪变严重。ALT、AST、TC、TG增加。干预组小鼠与模型组相比体重、肝重无明显差异;HE染色显示脂肪变减轻,ALT降低。结论 rhIL-1RA能有效减轻小鼠脂肪肝的炎症反应,减轻肝损伤。
Objective To investigate the effect of rhIL-1 RA on inflammation induced by MCD diet in NASH mice and its mechanism. Methods Ninety-five 5-week-old SPF mice were randomly divided into three groups: normal control group, model group and intervention group. Each group received 30 animals, which were given normal SPF feed for 1 week. They were fed with MCS feed. Normal control mice, while using the MCD feed-fed model group,the intervention group of mice, all mice were routinely given normal drinking water daily. The mice in the model group were intraperitoneally injected with 1 mL of normal saline daily. The mice in the intervention group were intraperitoneally injected with human recombinant interleukin-1 receptor antagonist 20 mg/kg daily for 4 weeks. The body weight, liver weight, liver function and blood lipids of the mice were measured, and HE staining was performed on the liver tissues to observe the pathological changes. Results After the end of the experiment, the body weight and liver weight of the model group were reduced compared with the normal group. HE staining showed that the fat became severe. ALT, AST, TC, TG increased. There was no significant difference in body weight and liver weight between the intervention group and the model group; HE staining showed a decrease in steatosis and a decrease in ALT. Conclusion RhIL-1 RA can effectively alleviate the inflammatory response of fatty liver in mice and alleviate liver injury.
Objective To investigate the effect of rhIL-1 RA on inflammation induced by MCD diet in NASH mice and its mechanism. Methods Ninety-five 5-week-old SPF mice were randomly divided into three groups: normal control group, model group and intervention group. Each group received 30 animals, which were given normal SPF feed for 1 week. They were fed with MCS feed. Normal control mice, while using the MCD feed-fed model group,the intervention group of mice, all mice were routinely given normal drinking water daily. The mice in the model group were intraperitoneally injected with 1 mL of normal saline daily. The mice in the intervention group were intraperitoneally injected with human recombinant interleukin-1 receptor antagonist 20 mg/kg daily for 4 weeks. The body weight, liver weight, liver function and blood lipids of the mice were measured, and HE staining was performed on the liver tissues to observe the pathological changes. Results After the end of the experiment, the body weight and liver weight of the model group were reduced compared with the normal group. HE staining showed that the fat became severe. ALT, AST, TC, TG increased. There was no significant difference in body weight and liver weight between the intervention group and the model group; HE staining showed a decrease in steatosis and a decrease in ALT. Conclusion RhIL-1 RA can effectively alleviate the inflammatory response of fatty liver in mice and alleviate liver injury.
引文
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[8]朱稀雯.NASH中自噬通过TRAF6介导的泛素化抑制Kupffer细胞NLRP3炎症小体激活机制的研究[D].重庆医科大学,2017.
[2]陈玉强,汪年松.白介素受体拮抗剂在风湿性疾病中的应用及前景[J].世界临床药物,2012,33(02):74-77.
[3]史新龙.白细胞介素-1α及其受体拮抗剂对大肠癌细胞增殖、侵袭的影响[D].宁夏医科大学,2013.(下转第15页)10
[4]张忠涛,王宇.白细胞介素1β对大鼠肝细胞毒性作用的细胞内信号传导途径[J].中华外科杂志,2001(11):62-65.
[5]张慧芹,刘泽洲,续畅,等.小檗碱对胆碱-蛋氨酸缺乏饮食诱导非酒精性脂肪性肝炎小鼠肝组织巨噬细胞表型转化的调节作用[J].解剖学报,2014,45(05):633-638.
[6]周舟,陈小梅,李富强,等.活化胆碱能抗炎通路对非酒精性脂肪性肝炎炎症反应的抑制作用及其机制[J].中华肝脏病杂志,2015(1):64-68.
[7]李剑霜,陈芝芸,蒋剑平,等.胡柚皮黄酮对非酒精性脂肪性肝炎小鼠Th17/Treg平衡的调节作用[J].中国中药杂志,2015,40(13):2644-2648.
[8]朱稀雯.NASH中自噬通过TRAF6介导的泛素化抑制Kupffer细胞NLRP3炎症小体激活机制的研究[D].重庆医科大学,2017.