甲磺酸卡莫司他降低急性应激大鼠内脏敏感性和脊髓c-fos 表达

目的观察蛋白酶抑制剂（甲磺酸卡莫司他）对急性应激大鼠内脏敏感性的影响，探索肠道蛋白酶活性在急性应激引起内
脏高敏感性中的作用。方法采用急性束缚应激动物模型，在束缚应激前30 min口服甲磺酸卡莫司他或者生理盐水，观察大鼠
内脏敏感性变化、直肠粘膜和粪便中蛋白酶活性情况以及脊髓c-fos表达情况。结果口服不同剂量的甲磺酸卡莫司他后，大鼠
内脏敏感性均有降低，随着剂量的增加，内脏敏感性下降更明显，但是甲磺酸卡莫司他不能将急性应激大鼠组的内脏敏感性降
到应激前的水平。c-fos蛋白主要表达于脊髓背角浅层，口服不同剂量的甲磺酸卡莫司他后表达c-fos蛋白的阳性细胞数均减少
（P<0.05）。在30 mg/kg组，粪便和直肠粘膜中的蛋白酶活性较应激对照组下降，有统计学差异（P<0.05）。随着蛋白酶抑制剂浓
度的增加，蛋白酶活性下降更为明显，在100 mg/kg和300 mg/kg组，粪便和直肠粘膜中的蛋白酶活性较单纯应激组明显下降
（P<0.01）。结论肠道蛋白酶参与了急性应激大鼠内脏高敏感性，给予蛋白酶抑制剂后大鼠内脏敏感性和脊髓c-fos表达降低。

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

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.