大麻素1型受体在应激大鼠内脏敏感性调节中的作用

Effects of cannabinoid 1 receptor on regulation of visceral sensitivity in rats with acute restraint stress

目的研究大麻素1型受体（CBIR）对急性部分束缚应激大鼠内脏敏感性的调节作用。方法将30只Sprague-Dawley大鼠均分成空白对照组（假性应激）、应激对照组和激动剂组。于实验第1、2、5、8天以测定结直肠气囊扩张（CRD）后腹壁肌电图（EMG）放电频率表示大鼠内脏感觉功能的变化。通过RT-PCR方法检测实验第8天各组肠道CB1RmRNA表达水平。结果实验第1天，三组大鼠腹壁肌电放电频率基础值差异均无统计学意义（P值均〉0．05）。实验第2天，激动剂组大鼠在40、60、80mmHg（1mm Hg=0．133kPa）压力下的腹壁肌电放电频率[分别为（22．37±1．49）、（42．24±3．03）、（69．09±5．54）次/min]较应激对照组大鼠[分别为（39．71±1．84）、（84．45±8．85）、（112．56±11.66）次／mini显著降低（P〈0．05）。实验第5天，应激对照组大鼠在40、60、80mmHg压力下的腹壁肌电放电频率[分别为（104．12±6．77）、（158．07±18．68）、（193．58±25．69）次／mini较空白对照组[分别为（36．33±5．42）、（74．07±8．25）、（102．94±7．95）次/min]和激动剂组[分别为（74．66±6．44）、（140．10±4．68）、（160．39±5．60）次min]增多，差异均有统计学意义（P值均〈0．05）。实验第8天各组大鼠同一压力下的腹壁肌电放电频率差异均无统计学意义（P值均〉0．05）。应激对照组大鼠回盲部、近端结肠和远端结肠CB1RmRNA表达水平（分别为2．53±0．52、2．29±0．42、2．54±0．29）均显著高于空白对照组（分别为0．56±0．15、0．73±0．12、0．82±0．09），差异均有统计学意义（P值均〈0．05）。CB1R激动剂干预对大鼠肠道CB1RmRNA表达无影响。结论CB1R在束缚应激所致大鼠内脏高敏感中起重要的保护性调节作用。

Objective To investigate the effects of cannahinoid 1 receptor （CBIR） on regulating visceral sensitivity in rats with acute partial restraint stress. Methods Thirty Sprague Dawley rats were divided into blank control （sham stress）, acute stress and CB1R groups with 10 each. The frequency of discharge of electromyogram （EMG） was recorded at the 1st, 2nd, 5th and 8th day to evaluate the visceral sensitivity to colorectal distension （CRD） in rats. The expression of the CB1R mRNA was determined by means of RTPCR at day 8. Results There was no significant difference in baseline discharge frequency among three groups at the 1st day. But the discharge frequencies corresponding to CRD at 40,60,80 mm Hg at the 2nd day were significantly lower in CB1R group 5（22.37±1. 49）/min, （42. 24±3. 03）/min and （69. 09±5. 54）/min, respectively] than in acute stress group [（39. 71±1.84）/min,（84. 45±8.85）/min and （112. 56±11. 66）/min, respectively, P〈0.05）]. The discharge frequencies corresponding to CRD at 40,60,80 mm Hg in acute stress group E（104.12±6.77）/min, （158. 07±18.68）/min, （193.58±25.69）/min,respectively] showed a significant elevation at the 5th day in comparison with blank control group[（36. 33 ± 5. 42）/min, （74.07±8.25）/min,（102. 94±7.95）/min, respectively, P 〈0. 051 or CB1R group [（74. 66± 6.44）/min,（140.10±4.68）/min and （160.39±5.60）/min,respectively, P 〈0.05]. However, at the 8th day after stress, there was no significant difference in discharge frequency among three groups. The expressions of CB1R mRNA in ileocecal junction, proximal colonic and distal colonic tissues were significantly higher in acute stress group （2.53±0.52, 2.29±0.42, 2.54±0.29 respectively） than in blank control group（0.56±0.15, 0. 73±0.12, 0. 82±0. 09, respectively, P〈0.05）. There was no effect of CB1R agonist on CB1R mRNA expression in rats. Conclusion The visceral sensitivity in rats induced by stress can trigger the accommodation of endogenous cannabinoid system that plays an important role in modulation of visceral sensitivity.