Protective effect of simvastatin on impaired intestine tight junction protein ZO-1 in a mouse model of Parkinson’s disease

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• 作者：Xin Fang ; Ren-shi Xu
• 关键词：duodenum ; colon ; simvastatin ; tight junction protein ; matrix metallopeptidase 9
• 刊名：Journal of Huazhong University of Science and Technology [Medical Sciences]
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：35
• 期：6
• 页码：880-884
• 全文大小：1,192 KB
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• 作者单位：Xin Fang (1)
  Ren-shi Xu (1)
  
  1. Department of Neurology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China
  
• 刊物主题：Medicine/Public Health, general;
• 出版者：Springer Berlin Heidelberg
• ISSN：1993-1352

文摘

Recently, several studies showed that gastrointestinal tract may be associated with pathophysiology of Parkinson’s disease (PD). Intestine tight junction protein zonula occluden-1 (ZO-1) is an important component of intestinal barrier which can be degraded by matrix metallopeptidase 9 (MMP-9). In our previous study, a significant decline in ZO-1 was observed along with enhanced MMP-9 activity in the duodenum and distal colon of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. In this study, the protective effect of simvastatin on ZO-1 was investigated using an MPTP mouse model of PD. Seven days after the end of MPTP application, the expression level of ZO-1 was evaluated by immunohistochemistry. The protein expression levels of ZO-1 and MMP9 were detected by Western blotting. Meanwhile, MMP-9 activity was analyzed by gelatin zymography. MPTP treatment led to a decrease in the expression of ZO-1, which was accompanied by elevated MMP-9 activity. Treatment with simvastatin could partly reverse the MPTP-induced changes in ZO-1 expression and reduce MMP-9 protein and activity. Taken together, these findings suggest that simvastatin administration may partially reverse the impairment of ZO-1 induced by MPTP via inhibiting the activity of MMP9, fortify the impaired intestinal barrier and limit gut-derived toxins that pass across the intestinal barrier. Key words duodenum colon simvastatin tight junction protein matrix metallopeptidase 9