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基质金属蛋白酶9和血管舒张刺激磷蛋白与重症急性胰腺炎大鼠急性肾损伤的关系

Matrix Metalloproteinase 9 and Vasodilator-Stimulated Phosphoprotein Related to Acute Kidney Injury in Severe Acute Pancreatitis Rats.

作者信息

Li Haitao, Liu Jianqiang, Wang Wen, Zhang Zhijian, Li Dazhou, Lin Kerong, Chen Zhiping, Lin Wulian

机构信息

Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzong Clinical Medical College of Fujian Medical University, 165 Xi'erhuan North Road, Fuzhou, 350025, Fujian Province, China.

出版信息

Dig Dis Sci. 2015 Dec;60(12):3647-55. doi: 10.1007/s10620-015-3820-8. Epub 2015 Aug 12.

Abstract

BACKGROUND

Severe acute pancreatitis (SAP) usually results in acute renal failure. Matrix metalloproteinase 9 (MMP-9) and vasodilator-stimulated phosphoprotein (VASP) may participate in disease progression.

AIM

To investigate the renal expression of MMP-9 and VASP in SAP rats with acute kidney injury.

METHODS

A total of 100 rats were randomly assigned to sham 6-h, sham 12-h, sham 24-h, sham 36-h, sham 48-h, SAP 6-h, SAP 12-h, SAP 24-h, SAP 36-h, and SAP 48-h treatment groups (n = 10 per group). Levels of serum amylase (AMY), creatinine (Cr), and blood urea nitrogen (BUN) were determined. Renal pathology and ultrastructural examinations were performed, and renal mRNA and protein expression of MMP-9 and VASP were determined by real-time RT-PCR and Western blot, respectively. The activity of MMP-9 was assessed by gelatin zymography.

RESULTS

In the SAP groups, serum levels of AMY, Cr, and BUN were markedly higher than in the sham groups. The peak value of AMY was observed from 12 to 24 h, but that of Cr and BUN was observed at 36 h. Capillary endothelial cells in the renal interstitium were impaired and expression of MMP-9 and VASP in the kidney was significantly increased when compared with the sham groups. Expression of MMP-9 and VASP declined when renal damage reached a maximum after 24 h.

CONCLUSIONS

In the presence of acute kidney injury in SAP, the renal expression of MMP-9 and VASP is related to damage of endothelial cells in capillaries, which reached a maximum at 24 h and declined afterwards.

摘要

背景

重症急性胰腺炎(SAP)通常会导致急性肾衰竭。基质金属蛋白酶9(MMP-9)和血管舒张刺激磷蛋白(VASP)可能参与疾病进展。

目的

研究急性肾损伤的SAP大鼠肾脏中MMP-9和VASP的表达。

方法

将100只大鼠随机分为假手术6小时组、假手术12小时组、假手术24小时组、假手术36小时组、假手术48小时组、SAP 6小时组、SAP 12小时组、SAP 24小时组、SAP 36小时组和SAP 48小时组(每组n = 10)。测定血清淀粉酶(AMY)、肌酐(Cr)和血尿素氮(BUN)水平。进行肾脏病理和超微结构检查,并分别通过实时RT-PCR和蛋白质印迹法测定肾脏中MMP-9和VASP的mRNA和蛋白质表达。通过明胶酶谱法评估MMP-9的活性。

结果

在SAP组中,AMY、Cr和BUN的血清水平明显高于假手术组。AMY的峰值出现在12至24小时,但Cr和BUN的峰值出现在36小时。与假手术组相比,肾间质中的毛细血管内皮细胞受损,肾脏中MMP-9和VASP的表达显著增加。24小时后肾损伤达到最大值时,MMP-9和VASP的表达下降。

结论

在SAP合并急性肾损伤时,肾脏中MMP-9和VASP的表达与毛细血管内皮细胞损伤有关,在24小时达到最大值,随后下降。

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