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甲磺酸卡莫司他,一种蛋白酶抑制剂,可抑制急性束缚应激大鼠的内脏敏感性和脊髓c-fos表达。

[Camostat mesilate, a protease inhibitor, inhibits visceral sensitivity and spinal c-fos expression in rats with acute restraint stress].

作者信息

Zhao Juhui, Wang Zongyan, Zou Baicang, Song Yahua, Dong Lei

机构信息

Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.E-mail:

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2014 Oct;34(10):1546-50.

Abstract

OBJECTIVE

To observe the effect of gut protease activity on visceral hypersensitivity in rats with acute restraint stress.

METHODS

Sprague-Dawley rats were given 30, 100 or 300 mg/kg camostat mesilate (CM), a protease inhibitor, or saline intragastrically 30 min before acute restraint stress induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk for 2 h. Visceral perception of the rats was quantified as the visceral motor response with an electromyography, and the rectal mucosa and feces protease activity and spinal c-fos expression were measured.

RESULTS

CM dose-dependently reduced visceral sensitization elicited by rectal distension, but these doses did not completely inhibit stress-induced visceral sensitization. In normal rats, c-fos expression was found mainly in the superal spinal cord dorsal horn, and after the administration the CM, c-fos-positive cells decreased significantly in all dose groups (P<0.05). In 30 mg/kg CM group, fecal and rectal mucosal protease activity significantly decreased as compared with that in the stress group (P<0.05), and as CM dose increased to 100 and 300 mg/kg, the protease activity decreased even further (P<0.01).

CONCLUSION

The gut protease is involved in acute stress-induced visceral hypersensitivity, and CM can lower the visceral sensitivity and spinal c-fos expression in rats.

摘要

目的

观察肠道蛋白酶活性对急性束缚应激大鼠内脏高敏感性的影响。

方法

将Sprague-Dawley大鼠在通过包裹前肩部、上前肢和胸段躯干诱导2小时急性束缚应激前30分钟,分别给予30、100或300mg/kg的蛋白酶抑制剂甲磺酸加贝酯(CM)或生理盐水灌胃。大鼠的内脏感觉通过肌电图以内脏运动反应进行量化,并测量直肠黏膜和粪便中的蛋白酶活性以及脊髓c-fos表达。

结果

CM剂量依赖性地降低了直肠扩张引起的内脏致敏,但这些剂量并未完全抑制应激诱导的内脏致敏。在正常大鼠中,c-fos表达主要在脊髓背角上部发现,给予CM后,所有剂量组的c-fos阳性细胞均显著减少(P<0.05)。在30mg/kg CM组中,与应激组相比,粪便和直肠黏膜蛋白酶活性显著降低(P<0.05),随着CM剂量增加到100和300mg/kg,蛋白酶活性进一步降低(P<0.01)。

结论

肠道蛋白酶参与急性应激诱导的内脏高敏感性,CM可降低大鼠的内脏敏感性和脊髓c-fos表达。

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