内源性大麻素系统调节大鼠内脏感觉的研究

Modulation of endocannabinoid system on visceral hypersensitivity in rat model of acute restraint stress

目的探讨大麻素系统对内脏感觉功能的调节机制。方法选取SD大鼠24只随机分为对照组、急性束缚溶媒组(溶媒组)、急性束缚加激动剂组(激动剂组)和急性束缚加拮抗剂组(拮抗剂组),每组各6只;采用急性束缚应激SD大鼠模型,腹腔注射大麻素受体1(CB1)激动剂(1319ACEA)和拮抗剂(SR141716A),记录不同结直肠扩张(CRD)压力下腹壁外斜肌活动水平;采用免疫印迹法(WB)检测大鼠模型不同肠段黏膜组织的一氧化氮合酶(nNOS)蛋白表达水平。结果拮抗剂组、激动剂组、溶媒组、对照组在CRD压力(60mmHg)条件下,腹壁外斜肌活动水平依次为(158.0±3.20)、(119.57±13.58)、(131.77±20.61)、(102.86±34.96);在CRD压力(80 mmHg)条件下为(219.01±12.97)、(178.83±22.16)、(181.95±32.72)、(153.77±38.10),拮抗剂组的腹壁外斜肌活动水平均高于其他组(P<0.05)。急性束缚组回盲部、近端结肠、远端结肠黏膜nNOS蛋白表达水平明显低于对照组[(0.58±0.0)vs(70.71±0.08)、(0.54±0.10)vs(0.68±0.08)、(0.59±0.08)vs(0.72±0.09),P<0.01]。结论内源性大麻素系统通过CB1受体调节其抗内脏伤害性刺激和抗痛觉过敏作用,nNOS活性下调与内脏感觉高敏感有关。

Objective To explore the modulation of endoeannabinoid system on visceral sensation in rat. Methods Twenty-four rats were divided into 4 groups：control, acute restraint stress with vehicle, acute restraint stress with agonist, acute restraint stress with antagonist. The acute restraint stress model of rat were established, ve- hicle, 1319ACEA and SR141716A were administrated by intraperitoneal injection, then colorectal distension（ CRD ） were conducted and abdominal electromyogram in response to CRD was recorded. The expression of nNOS in ileoce-cum and colon mueosa was assessed by western blotting. Results The frequence of electrical activity of abdominal extemal oblique muscle of rat model of acute restraint stress with administration with SR141716A intraperitoneally sig- nificantly higher than those of other 3 groups in CRD of 60mmHg and 80 mmHg [ （158.0 ± 3.20）, （119.57 ± 13.58） ,（131.77 ± 20.61 ）, （ 102. 86 ±34.96） ; （219.01 ± 12.97）, （ 178. 83 ± 22. 16）, （ 181.95 ± 32.72）, （153.77 ±38. 10） ,P 〈0. 05] ;The expression of nNOS in mucosa of ileocecum and proximal and distal colon in rat model of acute restraint stress was significantly lower than those in control [ （0. 58 ±0. 0） vs （70. 71±0. 08）, （0. 54 ± 0. 10） vs （ 0. 68 ± 0. 08）, （0.59 ±0. 08 ） vs （0. 72 ±0. 09 ）, P 〈 0.01 ]. Conclusion The endoeannabinoid system may modulate visceral hypersensitivity by CB1 receptor. The down regulation of activity of nNOS was associated with visceral hypersensitivity.