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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-HT_(2A) receptor,5-HT_(2A)R)、5-羟色胺7受体(5-HT_7receptor,5-HT_7R)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(2μg/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-HT_(2A)R、5-HT_7R和TRPV1的表达。结果当气囊压力在40、60、80 mm Hg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 mm Hg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-HT_(2A)R、5-HT_7R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-HT_(2A)R、5-HT_7R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-HT_(2A)R、5-HT_7R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-HT_(2A)R、5-HT_7R和TRPV1表达有关。
Objective To investigate the effect of gongtai on the expression of 5-HT2 (2A) receptor and 5-HT2 (2A) R in the dorsal root ganglion of irritable bowel syndrome (IBS) , 5-HT_7 receptor (5-HT_7R) and transient receptor potential vanilloid type-1 (TRPV1) Methods Sixty newborn SD rats were randomly divided into blank control group, model control group, positive drug control group, low dose intestine group, middle dose group and high dose group, with 10 rats in each group. Alzheimer’s rectal acetic acid stimulation was used to establish visceral hypersensitivity rat model. The positive control drug was injected intraperitoneally (2μg / g) into the capsazepine (TRPV1 blocker) half an hour before acetic acid stimulation in the control group. The other groups (except the blank control group) were injected intraperitoneally with the same volume of solvent. Four weeks after the end of modeling, low dose (2.5 g / kg), middle dose (5 g / kg) and high dose (10 g / kg) , Model control group and positive control group were given equal volume of deionized water gavage. After 4 weeks of treatment, abdominal withdrawal reflex (AWR) score was recorded by colorectal balloon dilatation to evaluate the visceral sensitivity of rats in each group. The expression of 5-HT 2A R, 5-HT 7 R and TRPV 1 in the spinal dorsal root ganglion of IBS visceral sensitive rats was detected by immunohistochemistry. Results When the balloon pressure was 40, 60, 80 mm Hg, the AWR score of the model control group was significantly higher than that of the blank control group (P <0.01). When balloon pressure was at 40 and 60 mm Hg, the AWR score of each dose group in GITT group was significantly lower than that of the model control group (P <0.05, P <0.01); in model control group, 5-HT_ 2A) R, 5-HT7R and TRPV1 expression were significantly higher than those in the blank control group (P <0.01). Compared with the model control group, the 5-HT2R, 5-HT7R (P <0.01). The expression of 5-HT_ (2A) R, 5-HT_7R and TRPV1 in the DRG ganglion at the high dose of Gitai Taigui had no significant difference with that of the blank control group (P> 0.05) . Conclusion Gengtai can reduce the visceral sensitivity of IBS, and its mechanism may be related to the decrease of 5-HT 2A R, 5-HT 7R and TRPV 1 in the dorsal root ganglion.