桑枝多糖预防性给药对肾缺血再灌注损伤模型小鼠炎症反应的影响及机制研究  

Study on the Effects of Prophylactic Administration of Ramulus mori Polysaccharides on Inflammatory Responses of Renal Ischemia Reperfusion Injury Model Mice and Its Mechanism

作　　者：黄倩 林佩璜 郑丹丹 黄秋虹 王梅爱 陈慧勤 施子禄[2] HUANG Qian;LIN Peihuang;ZHENG Dandan;HUANG Qiuhong;WANG Meiai;CHEN Huiqin;SHI Zilu(Teaching and Research Section of Physiology,Basic Medicine Department,Quanzhou Medical College,Fujian Quanzhou 362100,China;Dept.of Nephrology,Quanzhou First Hospital of Fujian Medical University,Fujian Quanzhou 362000,China)

机构地区：[1]泉州医学高等专科学校基础医学部生理教研室,福建泉州362100 [2]福建医科大学附属泉州第一医院肾内科,福建泉州362000

出　　处：《中国药房》2019年第13期1786-1791,共6页China Pharmacy

基　　金：国家自然科学基金面上项目(No.31471100);浙江省自然科学基金资助项目(No.LY13H070002);泉州市科技计划项目(No.2018Z179)

摘　　要：目的:研究桑枝多糖(RMP)预防性给药对肾缺血再灌注损伤(RIRI)模型小鼠炎症反应的影响及可能的作用机制。方法:将60只C57BL/6小鼠随机分为假手术组、模型组、阿托伐他汀组(阳性对照,15mg/kg)和RMP低、中、高剂量组(300、600、1200mg/kg)。除假手术组外,其余5组小鼠复制RIRI模型。术前24h灌胃给药,每天给药1次,连续给药1周。再灌24h后处死各组小鼠,检测其血清中肌酐(Scr)、尿素氮(BUN)水平;光镜下观察其肾脏病理组织学变化;采用酶联免疫吸附法测定其血清中白细胞介素1β(IL-1β)、IL-6、IL-10和肿瘤坏死因子α(TNF-α)水平;采用Westernblot法测定其肾皮质中Toll样受体4(TLR4)、p38丝裂原活化蛋白激酶(p38MAPK)和磷酸化p38MAPK(p-p38MAPK)蛋白表达。结果:与假手术组比较,模型组小鼠血清中Scr、BUN水平明显升高(P<0.01);肾组织出现典型的炎性改变,肾小管上皮细胞大量变性、坏死,并见炎性细胞浸润;血清中IL-1β、IL-6、IL-10和TNF-α水平明显升高(P<0.01);肾皮质中TLR4、p38MAPK和p-p38MAPK蛋白表达水平明显升高(P<0.01)。与模型组比较,各给药组大鼠血清中Scr、BUN水平均明显降低(P<0.05或P<0.01);肾组织病理损伤均不同程度改善,尤以RMP中、高剂量组改善最为明显;各给药组小鼠血清中IL-1β、IL-6水平均明显降低(P<0.05或P<0.01),阿托伐他汀组和RMP高剂量组小鼠血清中IL-10水平进一步升高(P<0.01),阿托伐他汀组和RMP中、高剂量组小鼠血清中TNF-α水平明显降低(P<0.05或P<0.01);各给药组小鼠肾皮质中TLR4、p-p38MAPK蛋白表达水平显著降低(P<0.05或P<0.01)。结论:RMP预防性给药能改善小鼠RIRI,其机制可能与通过抑制TLR4/p38MAPK通路,进而减轻炎症反应有关。OBJECTIVE:To study on the effects of prophylactic administration of Ramulusmoripolysaccharides(RMP)on inflammatory response of renal ischemia reperfusion injury(RIRI)model mice and to explore its possible mechanism.METHODS:Totally 60 C57BL/6 mice were randomly divided to sham operation group,model group,atorvastatin group(positive control,15 mg/kg),RMP low-dose,medium-dose and high-dose groups(300,600,1 200 mg/kg).Except for sham operation group,RIRI model was induced in other 5 groups.24 h before surgery,they were given relevant medicine intragastrically,once a day,for consecutive one week.24 h after reperfusion,the mice were sacrificed.The serum levels of Scr and BUN were detected.The morphological changes of renal tissue were observed under optical microscope.The serum levels of IL-1β,IL-6,IL-10 and TNF-αwere determined by ELISA.Western blot assay was used to determine the protein expressions of Toll-like receptor 4(TLR4),p38 mitogen-activation protein kinase(p38MAPK)and p-p38MAPK.RESULTS:Compared with sham operation group,the serum levels of Scr and BUN were significantly elevated in model group(P<0.01).RIRI led to typical inflammatory response of renal tissue,widespread renal tubular epithelial cell degeneration and necrosis,and inflammatory cells infiltration.Serum levels of IL-1β,IL-6,IL-10 and TNF-αwere increased significantly(P<0.01).The protein expressions of TLR4,p38MAPK and p-p38MAPK were increased significantly in renal cortex(P<0.01).Compared with model group,serum levels of Scr and BUN were decreased significantly in administration groups(P<0.05 or P<0.01).The pathological damage of renal tissue was improved in varying degrees,especially in the RMP medium-dose and high-dose groups.Serum levels of IL-1βand IL-6 were decreased significantly in administration groups(P<0.05 or P<0.01).Serum levels of IL-10 were further increased in atorvastatin group and RMP high-dose group(P<0.01),and serum level of TNF-αwas decreased significantly in atorvastatin group and RMP medium-dose and high-dose groups(P

关 键 词：桑枝多糖 肾缺血再灌注损伤 TOLL样受体4 P38丝裂原活化蛋白激酶 白细胞介素6 白细胞介素10 小鼠 

分 类 号：R965[医药卫生—药理学]