1. 上海中医药大学附属曙光医院消化科,上海,200021
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LI Li, CONG Jun, ZHANG Zheng-li, et al. Effects of “Chang Ji Tai” on 5-HT2AR, 5-HT7R and TRPV1 of dorsal root ganglia in irritable bowel syndrome rats of visceral hypersensitivity. [J]. Shanghai Journal of Traditional Chinese Medicine 50(6):80-84(2016)
目的:研究肠吉泰对肠易激综合征(irritable bowel syndrome,IBS)内脏敏感大鼠脊髓背根神经节 5-羟色胺2A受体(5-HT2A receptor,5-HT2AR)、5-羟色胺7受体(5-HT,7, receptor,5-HT,7,R)和 瞬时感受器电位香草酸受体1(transient receptor potential vanilloid type-1,TRPV1)表达的影响。 方法:60只新生SD大鼠随机分成空白对照组、模型对照组、阳性药对照组、肠吉泰低剂量组、中剂量组和高剂量组,每组10只。采用Al-chaer直肠醋酸刺激法建立内脏高敏感性大鼠模型。造模期间阳性药对照组大鼠醋酸刺激前半小时给予capsazepine(TRPV1阻断剂)腹腔注射(2 μg/g),其余各组(除空白对照组外)均给予相同体积的溶剂腹腔注射。造模结束4周后,肠吉泰各治疗组每日分别给予低剂量(2.5 g/kg)、中剂量(5 g/kg)和高剂量(10 g/kg)中药灌胃,空白对照组、模型对照组和阳性药对照组每日分别给予等量去离子水灌胃。治疗4周后,采用结直肠气囊扩张法记录大鼠的腹部回缩反射(abdominal withdrawal reflex,AWR)计分来评估各组大鼠的内脏敏感性。并用免疫组化法检测IBS内脏敏感大鼠脊髓背根神经节5-HT2AR、5-HT,7,R和 TRPV1的表达。 结果:当气囊压力在40、60、80 mmHg时,模型对照组AWR评分显著高于空白对照组(P,<,0.01)。当气囊压力在40、60 mmHg时,肠吉泰各剂量治疗组AWR评分较模型对照组明显降低(P,<,0.05,P,<,0.01);模型对照组大鼠脊髓背根神经节5-HT2AR、5-HT,7,R和 TRPV1表达较空白对照组明显增高(P,<,0.01);与模型对照组比较,肠吉泰各剂量组背根神经节的5-HT2AR、5-HT,7,R 和 TRPV1表达明显下降(P,<,0.01);肠吉泰高剂量组脊髓背根神经节的5-HT2AR、5-HT,7,R 和 TRPV1表达,与空白对照组无明显差异(P,>,0.05)。 结论:肠吉泰能降低IBS内脏敏感性,其机制可能与降低脊髓背根神经节5-HT2AR、5-HT,7,R 和TRPV1表达有关。
Objective:To study the effects of “Chang Ji Tai” on 5-HT2A receptor (5-HT2AR), 5-HT,7, receptor (5-HT,7,R) and transient receptor potential vanilloid type-1(TRPV1) of dorsal root ganglia in irritable bowel syndrome(IBS) rats of visceral hypersensitivity. MethodsSixty neonatal Sprague-Dawley rats were randomly divided into 6 groups:normal control group, model control group, positive control group, “Chang Ji Tai” low-dose group, middle-dose group and high-dose group. The IBS rats model of visceral hypersensitivity was induced by intrarectal acetic acid irritation in the latter 5 groups. During the period of making model capsazepine (TRPV1 antagonist) was intraperitoneally injected (2 μg/g) in positive control group 30 min before intrarectal irritation. Four weeks after the end of modeling, “Chang Ji Tai” with concentrations of respectively 2.5 g/kg, 5 g/kg and 10 g/kg were administered intragastrically every day in “Chang Ji Tai” each dose group respectively, while equivalent deionized water was administered intragastrically in the other three groups. After 4-week treatment, rectal balloon distension was applied to evaluate visceral hypersensitivity by score of abdominal withdrawal reflex (AWR). The levels of 5-HT2AR, 5-HT,7,R and TRPV1 in dorsal root ganglia were detected by immunohistochemistry. Results:Compared with the normal control group, the scores of AWR with the 40,0 and 80 mmHg pressure were significantly higher in model control group (P,<,0.01). Compared with the model control group, the scores of AWR with the 40 and 60 mmHg pressure were significantly lower in all “Chang Ji Tai” groups (P,<,0.05, P,<,0.01). The expressions of 5-HT2AR, 5-HT,7,R and TRPV1 of dorsal root ganglia in model control group were significantly higher than that in the normal control group (P,<,0.01). The expressions of 5-HT2AR, 5-HT,7,R and TRPV1 of dorsal root ganglia in all “Chang Ji Tai” groups were significantly lower than that in model control group (P,<,0.01). There was no significant difference between “Chang Ji Tai” high-dose group and normal control group in the levels of 5-HT2AR, 5-HT,7,R and TRPV1 of dorsal root ganglia (P,>,0.05). Conclusion: “Chang Ji Tai” can reduce the visceral hypersensitivity by regulating the expressions of 5-HT2AR, 5-HT,7,R and TRPV1 of dorsal root ganglia.
肠吉泰内脏高敏感5-羟色胺2A受体5-羟色胺7受体瞬时感受器电位香草酸受体1
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