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白石汤治疗腹泻型肠易激综合征(肝郁脾虚证)的临床与实验研究

Clinical and Experimental Research on Treating Diarrhea IBS Caused by Hepatic Stasis, Spleen Deficiency by Applying Baishi Decoction

【作者】 李德锋

【导师】 周晓虹;

【作者基本信息】 南京中医药大学 , 中医内科学, 2011, 硕士

【摘要】 第一部分临床研究目的:运用白石汤治疗腹泻型肠易激综合征(肝郁脾虚证),观察治疗前后腹痛或腹部不适、大便次数、大便溏稀等症状的变化情况,评价白石汤治疗腹泻型肠易激综合征的临床疗效。方法:1.选择符合纳入标准的肝郁脾虚腹泻型肠易激综合征患者60例,随机分为中药白石汤治疗组30例、西药得舒特对照组30例。2.治疗组采用白石汤治疗(炒白术20g,石菖蒲6g,地榆15g,乌梅6g,仙鹤草15g,肉豆蔻10g),每日1剂,煎2次,于早、晚餐后30分钟服用。对照组口服得舒特50mmg,每日3次。两组均以连续用药8周为一疗程。3.比较两组治疗前后症状总积分、综合疗效及治疗前后各临床症状积分,作出综合评定。结果:(1)总体临床疗效方面:治疗组30例中,临床痊愈11例,显效13例,有效4例,无效2例,总有效率为93.3%;对照组30例中,临床痊愈2例,显效8例,有效11例,无效9例,总有效率为70.0%。治疗组的总体临床疗效明显优于对照组(p<0.01)。(2)两组治疗前后总积分比较均有显著性差异(P<0.01),提示治疗组与对照组对改善临床症状均有明显作用。治疗后治疗组与对照组比较症状总积分有显著性差异(p<0.01),说明治疗组对临床症状的改善明显优于对照组。(3)治疗组对改善肠鸣矢气、腹胀症状与对照组疗效相当(P>0.05),对食欲不振的疗效优于对照组(P<0.05),对腹痛、腹部不适、腹痛欲泻、泻后痛减、大便次数、大便溏稀及情绪抑郁或烦躁易怒的疗效明显优于对照组(p<0.01)。结论:白石汤治疗IBS-D肝郁脾虚证能明显改善其临床症状,疗效优于对照组。从临床角度验证了白石汤是治疗IBS-D的有效方剂。第二部分实验研究目的:观察白石汤对大鼠肠粘膜肥大细胞(MC)活化、脱颗粒情况及5-HT表达的影响。方法:将26只SD大鼠随机分成空白对照组、模型组、西药组、中药高剂量组、中药低剂量组5组,空白对照组3只,西药组5只,其余每组各6只。实验前10h禁食,自由饮水。各组大鼠采用生大黄煎液灌胃和束缚应激刺激法造模。空白对照组:不予造模,不予以任何药物干预;模型组:按上法造模后,予以0.9%生理盐水灌胃,10ml/Kg,2次/日,连续一周;中药高剂量组使用35%浓度颗粒剂灌胃,1.22g/次,2次/‘日;中药低剂量组使用10.5%浓度颗粒剂灌胃,0.31g/次,2次/日,连续一周;西药组:以得舒特按30mg/kg灌胃,1次/日,连续一周。一周后分别脱颈椎处死各组大鼠,剖取大鼠直肠乙状结肠交界处粘膜,免疫组化法行MC甲苯胺蓝、类胰蛋白酶、c-fos染色及5-HT染色,进行相关病理观察,分析大鼠肠粘膜下层MC总数及活化数、5-HT指标值。结果:HE染色后与模型组相比,西药组大鼠肠粘膜组织炎症情况好转;与西药组相比中药组治疗后大鼠肠粘膜组织炎症改善更为明显;中药低剂量组、中药高剂量组相比,中药高剂量组疗效稍优,基本呈正常大鼠肠粘膜结构。经甲苯胺蓝染色、类胰蛋白酶免疫组化后显示,与模型组相比,中药低剂量、高剂量组均有显著性统计学意义(p<0.01);与空白组相比,模型组与西药组均有显著性统计学意义(p<0.01),中药低剂量、高剂量组无统计学意义(p>0.05)。经c-fos染色活化大鼠肠粘膜活化肥大细胞(MC)情况显示,与模型组相比,西药组无统计学意义(p>0.05),其他各组均有显著性统计学意义(p<0.01);西药组与中药低剂量、高剂量组比较均有显著性统计学意义(p<0.01),说明中药能减轻肠粘膜炎症程度,抑制炎症后肠粘膜肥大细胞(MC)的迁移生成,明显减少肠粘膜肥大细胞MC数量。5-HT染色结果显示,模型组与西药组及中药低剂量、高剂量组相比均有显著性统计学意义(p<0.01);西药组与中药低剂量组、高剂量组比较均有显著性统计学意义(p<0.0 1),说明中药能明显抑制大鼠肠粘膜5-HT的表达。结论:白石汤治疗腹泻型肠易激综合征的机理可能与减轻肠粘膜组织炎症、减少肠粘膜MC活化,降低5-HT表达有关。

【Abstract】 The first department:clinical researchObjectives:TO observe the clicial effects in treating Irritable Bowel Syndrome(IBS) With diarrhoea caused by hepatie stasis, Spleen deficiency with the decoction of baishi. To discuss its therapeutic action mechanism from the theory and the clinical effects.Methods:This research was based on 60 cases of outpatients with hepatie stasis, spleen deficiency from the clinic of the hospital attributed to TCM of Jiangsu Province.They were randomly divided in to two groups.One group was the treatment group,30 patients of which were treated with the decoction of baishi.The other group was the control group, with 30 patients being treated with Pinaverium bromide.These patients all met the TCM diagnosis criterion. Both groups were treated for eight weeks.Clinical symptoms’changes before and after treatment were detected respectively to evaluate the therapeutic effects.Results:After one course of treatment, significant difference was apparent in the clinical effects:In the treatment group,11 cases recovered and 13 cases significantly improved,4 cases improved,2 ineffcetual cases.The total effective rate in the treatment group is 93.3%.In the control group 2 cases recovered and 8 cases significantly improved,11 cases improved,9 ineffectual cases.The total effective rate in the control group is 70.0%.There was statistically significant difference in the total effective rate between the treatment group and control group(p<0.01).The effective rate from the treatment group is clearly superior.Conclusions:Above all, the decoction of baishi appears to have the significant effect in the treatment of IBS with diarrhoea caused by hepatic stasis and spleen deficiency,which is is clearly superior to he control group. The results demonstrate the practicality and feasibility.The second department:experimental researchObjectives:To explore mechanism of the decoction of baishi in curing experimental rat model of Irritable Bowel Syndrome(IBS) With diarrhoea caused by hepatie stasis, spleen deficiency by constructing animal model and observing correlated indexes(the cells of MC and 5-HT).The aim is to provide experimental evidence for clinical research.Methods:26 healthy wistar rats were randomly divided into five groups, control group had 3 rats, western medicine group had 5 rats, the other three group each had 6 rats.Diarrheal rats were established by intragastric administration with senna apozem and restraint-stress.2 weeks later when the models were established, the amount of decoction of baishi given to rats in large dose group and low dose group was 35g/kg weight and 10.5g/kg weight respectively.The amount of Pinaverium bromide given to control group was 30mg/kg weight. Two weeks later,all rats were killed to observe following index:cells of MC and 5-HT in small intestine and pathology of bowel tissue.Results:Contracted to model group between the western medicine group and the herb of low dose and high dose after dyeing of HE, The improvement of intestinal inflammation of the herb has significant effect superior to medicine.Contracted to model group between the medicine group and the herb of low dose and high dose after dyeing of toluidine blue and trypsin, the herb group has statistically significant (p<0.01). Contracted to the control group, the herb group has no statistically significant (p>0.05)Contracted to the western medicine group and the herb of low dose and high dose after dyeing of c-fos, the herb group has statistically significant (p<0.01). Contracted to the control group, the herb group has no statistically significant (p>0.05), while the western medicine group and model group all have statistically significant (p<0.01)Contracted to model group between the western medicine group and the herb of low dose and high dose after dyeing of 5-HT, the three groups all have statistically significant (p<0.01)It indicated there were significant therapeutic effects of the herb of baishi on improvement of intestinal inflammation by inhibiting the activation of intestinal MC and reducing the expression of 5-HT of the rats.Conclusions:The decoction of baishi can improve the intestinal pathology of the rats of IBS-D.The possible mechanism may be related to improve the intestinal inflammation by inhibitting the activation of intestinal MC and reducing the expression of 5-HT of the rats,which can help to achieve therapeutic purposes.

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