Sinomenine protects the kidney from ischemia reperfusion-induced apoptosis via up-regulation of microRNA-124 expression

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	Sinomenine protects the kidney from ischemia reperfusion-induced apoptosis via up-regulation of microRNA-124 expression
	Lyu, XH; Yang, YN; Wan, ZH; Ma, YQ; Leng, YF; Leng, YF (reprint author), Lanzhou Univ, Dept Anesthesiol, Hosp 1, 1 Dong Gang West Rd, Lanzhou 730000, Gansu, Peoples R China.
刊名	INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE
	2016
卷号	9 期号:10 页码:19185-19194
关键词	Sinomenine ischemia reperfusion injury microRNA-124 apoptosis caspase 9
ISSN号	1940-5901
文献子类	Article
英文摘要	Sinomenine (SIN), an alkaloid from Sinomenium acutum, has been used in the treatment of various inflammatory diseases including rheumatism and arthritis. However, the effect and mechanisms of sinomenine on kidneys from ischemia-reperfusion (I/R) injury have not been well understood. This study aimed to test whether sinomenine attenuate renal I/R injury and reveal its underlying molecular mechanism. Renal function, oxidative stress and related parameters were studied using a kidney I/R injury model in rats, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify apoptosis. MTT assay was used to detect the cell viability in HK-2 cells under hypoxia and re-oxygenation (H/R) conditions. Flow cytometry analysis was employed to measure apoptosis of H/R HK-2 cells. Expression of microRNAs was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and expression of caspase 9 was analyzed by Western Blot. In vivo experimental results showed that SIN significantly decreased the renal function as evidenced by decreasing the levels of serum creatinine (Cr), blood urea nitrogen (BUN) and activities of major markers of oxidative stress, i.e. malondialdehye (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO), and inhibited tubular epithelial apoptosis. In vitro experimental data further revealed that SIN directly guarded HK-2 cells from hypoxia-induced growth and apoptosis. In addition, RT-PCR analysis revealed that at 12 h post-injury, miR-320 and miR-378 were upregulated and miR-124, miR-21, miR-29 and miR-92a were downregulated in H/R HK-2 cells. Because miR-124 was one of the six miRNAs being most significantly downregulated, we investigated its function. Our study showed that the expression of miR-124 was significantly enhanced by SIN in H/R HK-2 cells in a dose-dependent manner and was dramatically decreased in mouse I/R injury kidney in a time-dependent manner. Furthermore, caspase 9 was identified as a direct target of miR-124 using a Luciferase reporter assay and western blot analysis. Following miR-124 silencing, SIN-induced cell viability and apoptosis were rescued in H/R HK-2 cells. Thus, SIN deserves further exploration as a novel agent to attenuate I/R injury.
学科主题	Research & Experimental Medicine
出版地	MADISON
语种	英语
WOS记录号	WOS:000391260400041
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/188628]
专题	第一临床医学院_期刊论文
通讯作者	Leng, YF (reprint author), Lanzhou Univ, Dept Anesthesiol, Hosp 1, 1 Dong Gang West Rd, Lanzhou 730000, Gansu, Peoples R China.
推荐引用方式 GB/T 7714	Lyu, XH,Yang, YN,Wan, ZH,et al. Sinomenine protects the kidney from ischemia reperfusion-induced apoptosis via up-regulation of microRNA-124 expression[J]. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE,2016,9(10):19185-19194.
APA	Lyu, XH,Yang, YN,Wan, ZH,Ma, YQ,Leng, YF,&Leng, YF .(2016).Sinomenine protects the kidney from ischemia reperfusion-induced apoptosis via up-regulation of microRNA-124 expression.INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE,9(10),19185-19194.
MLA	Lyu, XH,et al."Sinomenine protects the kidney from ischemia reperfusion-induced apoptosis via up-regulation of microRNA-124 expression".INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE 9.10(2016):19185-19194.