雌激素通过组胺H1受体调节内脏敏感性的机制研究

Study on mechanism of estrogen regulating visceral sensitivity via H1 receptor

目的研究雌激素在动物模型中对内脏敏感性的调节,探讨组胺H1受体(H1R)调节内脏敏感性的机制。方法8周龄雌性SD大鼠24只被切除双侧卵巢并埋置腹壁电极,7-10 d后分别给予以下干预:对照组(0.1 ml橄榄油+0.1 ml DMSO腹腔注射,不应激),单纯应激组(0.1 ml橄榄油+0.1 ml DMSO腹腔注射+急性束缚应激),雌二醇组(10μg/kg,溶于0.1 ml橄榄油腹腔注射+0.1 ml DMSO腹腔注射+急性束缚应激),雌二醇+H1R阻断剂组(雌二醇10μg/kg+H1R阻断剂Fexofenadine 20 mg/kg+急性束缚应激),每组6只在阶梯体积下直肠球囊扩张后检测大鼠内脏肌电活动。Western blot检测肠道组胺H1R的含量。用酶联免疫法检测各组大鼠血浆和肠道内组胺的含量,比较其含量变化。结果外源性雌二醇相比单纯应激能快速增加卵巢切除后应激大鼠VMR(P<0.05)。雌二醇+H1R阻断剂组VMR低于雌二醇组(P<0.01)。雌二醇组大鼠应激后肠道组胺水平高于应激组[(76.85±10.05)ng/g vs(42.85±7.78)ng/g,P<0.01],雌二醇+H1R阻断剂组肠道组胺水平[(68.58±10.40)ng/g]与雌二醇组无差异(P=0.34)。各组间血浆组胺水平无明显差异。各组间大鼠肠道H1R水平无明显差异。结论雌激素通过参与肠道组胺释放过程而调节内脏敏感性,而组胺可能通过受体H1R起作用。

Objective To study the effects of estrogen on visceral sensitivity in rat model and investigate the mechanism of histamine receptor H1R regulating the visceral sensitivity.Methods Twenty-four female adult 8-week-old SD rats were given bilateral ovariectomy(OVX)and implanted with electrodes into the abdominal wall.After 7 to 10 days,the rats were divided into control group(0.1 ml olive oil+0.1 ml DMSO,without stress),stress group(0.1 ml olive oil+0.1 ml DMSO+stress),estradiol group(10μg/kg diluted in 0.1 ml olive oil+0.1 ml DMSO+stress)and estradiol+H1R antagonist group(10μg/kg estradiol+20 mg/kg fexofenadine+stress).Six rats in each group underwent colorectal distension(CRD)with graded volumes of balloon to detect the visceral motor reflex(VMR).H1 receptor content in the colon was measured by Western blot.Histamine content in the serum and the colon was measured by ELISA.Results Compared with stress group,the VMR of rats was rapidly increased in estradiol group(P<0.05).VMR in estradiol+H1R antagonist group was lower than that in estradiol group(P<0.01).Colonic histamine content in estradiol group was higher than that in stress group[(76.85±10.05)ng/g vs(42.85±7.78)ng/g,P<0.01].No difference of colonic histamine content was found between estradiol group and estradiol+H1R antagonist group[(68.58±10.40)ng/g,P=0.34].No difference was found in the contents of plasma histamine and colonic H1R among four groups.Conclusion Estrogen could regulate the visceral sensitivity through histamine release,and histamine may play a role through its receptor H1R.