摘要
目的探讨组蛋白甲基化转移酶2(SMYD2)与顺铂致慢性肾脏病(CKD)炎症反应的相关性,为临床防治顺铂致CKD提供新方向。方法将16只小鼠分为对照组和顺铂组,每组8只。顺铂组小鼠给予10 mg/kg顺铂腹腔注射,对照组给予相同体积顺铂溶媒,1次/周,连续注射3周,第4周处死小鼠后收集血清和肾组织。全自动生化分析仪检测血尿素氮(BUN)和血肌酐(Scr);HE和Masson染色观察肾组织病理学改变;Western blot检测肾组织SMYD2、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)、E-钙黏素蛋白(E-cadherin)、纤维粘连蛋白(Fibronectin)、胶原蛋白3(Collagen-Ⅲ)、信号转导和转录激活因子3(STAT3)、p-STAT3、肿瘤坏死因子-α(TNF-α)和白细胞介素6(IL-6)的表达。结果与对照组相比,顺铂组小鼠BUN和Scr水平均明显升高(P<0.05),肾组织中部分肾小球出现系膜细胞增生,肾小管发生颗粒变性和空泡样变,肾间质纤维增生明显,SMYD2、α-SMA、Vimentin、Fibronectin、Collagen-Ⅲ、STAT3、p-STAT3、TNF-α、IL-6蛋白表达升高,E-cadherin蛋白表达下降(P<0.05);SMYD2与E-cadherin表达呈负相关,与α-SMA、Vimentin、Fibronectin、Collagen-Ⅲ、STAT3、p-STAT3、TNF-α、IL-6表达呈正相关(P<0.05)。结论SMYD2在顺铂致CKD小鼠肾组织中表达上调,推测其可能与STAT3信号通路共同介导炎症反应参与顺铂致CKD的发生发展。
Objective To explore the correlation between histone methyltransferase 2(SMYD2)and cisplatin-induced inflammatory response in chronic kidney disease(CKD),and provide a new direction for the clinical prevention and treatment of cisplatin-induced CKD.Methods Sixteen mice were divided into the control group and the cisplatin group according to the random number table method,with 8 mice in each group.Mice in the cisplatin group were injected intraperitoneally with 10 mg/kg cisplatin,and in the control group,the same volume of cisplatin solvent was injected once a week for 3 consecutive weeks.At the fourth week,the mice were sacrificed and serum and kidney tissue were collected.Automatic biochemical analyzer was used to detect blood urea nitrogen(BUN)and blood creatinine(Scr).HE and Masson staining was used to observe renal histopathological changes.Western blot assay was used to detect renal tissue SMYD2,α-smooth muscle actin(α-SMA),waveform protein(Vimentin),E-cadherin,Fibronectin,Collagen-Ⅲ,signal transducer and activator of transcription 3(STAT3),p-STAT3,tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Results Compared with the control group,the BUN and Scr levels were significantly increased in the cisplatin group(P<0.05).Some glomeruli in kidney showed mesangial cell proliferation,granular degeneration and vacuole-like changes in renal tubules.The proliferation of interstitial fibers was obvious.The expression levels of SMYD2,α-SMA,Vimentin,Fibronectin,Collagen-Ⅲ,STAT3,p-STAT3,TNF-αand IL-6 protein increased,and the protein expression of E-cadherin decreased(P<0.05).There was a negative correlation between SMYD2 and the expression of E-cadherin.There was a positive correlation bet-ween SMYD2 and expression levels ofα-SMA,Vimentin,Fibronectin,Collagen-Ⅲ,STAT3,p-STAT3,TNFa,and IL-6(P<0.05).Conclusion SMYD2 is upregulated in kidney of cisplatin-induced CKD mice.It is speculated that SMYD2 may be involved in the inflammation together with the STAT3 signaling pathway and participate in the occurrenc
作者
张妮
简久莹
王笑笑
余婷
陈思羽
郭兵
刘丽荣
ZHANG Ni;JIAN Jiu-ying;WANG Xiao-xiao;YU Ting;CHEN Si-yu;GUO Bing;LIU Li-rong(Center for Clinical Laboratories,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China;School of Clinical Laboratory Science,Guizhou Medical University;Department of Blood Transfusion,the First People's Hospital of Guiyang City;Guizhou Provincial Key Laboratory of Common Chronic Disease Pathogenesis and Drug Research,Guizhou Medical University)
出处
《天津医药》
CAS
北大核心
2021年第10期1048-1052,共5页
Tianjin Medical Journal
基金
国家自然科学基金资助项目(32060202)
贵州省高层次留学人才创新创业择优资助项目[留学人才择优资助合同(2018)01号]。
