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1.中国中医科学院 中药研究所,北京 100700
2.中国中医科学院 广安门医院,北京 100053
王娅杰,博士,副研究员,硕士生导师,从事中药药理学研究,E-mail:yjwang@icmm.ac.cn
朱晓新,研究员,博士生导师,从事中药药理学研究,E-mail:xxzhu@icmm.ac.cn
收稿日期:2021-03-05,
网络出版日期:2021-05-11,
纸质出版日期:2021-07-05
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王娅杰,崔羲和,陈颖等.戊己丸不同配伍方治疗肠易激综合征的比较[J].中国实验方剂学杂志,2021,27(13):1-9.
WANG Ya-jie,CUI Xi-he,CHEN Ying,et al.Therapeutic Efficacies of Wujiwan at Different Compatibilities in Treatment of Irritable Bowel Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(13):1-9.
王娅杰,崔羲和,陈颖等.戊己丸不同配伍方治疗肠易激综合征的比较[J].中国实验方剂学杂志,2021,27(13):1-9. DOI: 10.13422/j.cnki.syfjx.20211301.
WANG Ya-jie,CUI Xi-he,CHEN Ying,et al.Therapeutic Efficacies of Wujiwan at Different Compatibilities in Treatment of Irritable Bowel Syndrome[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(13):1-9. DOI: 10.13422/j.cnki.syfjx.20211301.
目的
2
从神经-免疫-内分泌网络对优选的2种戊己丸配伍方干预肠易激综合征(IBS)的作用特点进行比较研究,为中医辨证论治提供一定的理论依据。
方法
2
采用乳鼠结肠经皮冠状动脉腔内血管成形(PTCA)球囊刺激法建立IBS慢性高敏感动物模型,分为正常组、模型组、得舒特组、戊己丸1#和2#方高、中、低剂量组,其中1#方以0.67 g·kg
-1
为中剂量,2#方以0.77 g·kg
-1
为中剂量,加倍、减半分别为高、低剂量,得舒特给药剂量为0.01 g·kg
-1
。采用腹部抬起及弓背抬高阈值评价戊己丸不同配伍方对IBS肠道敏感性的影响;采用改良后的甲苯胺蓝染色法检测对大鼠结肠组织肥大细胞(MC)密度的影响;分别采用酶联免疫吸附测定(ELISA)和免疫组化法检测大鼠血液/结肠组织中5-羟色胺(5-HT),P物质(SP),生长抑素(SS)及血管活性肠肽(VIP)的浓度/阳性表达。
结果
2
各组大鼠体质量随时间差异无统计学意义;与正常组比较,模型组腹部抬起和弓背抬高阈值均显著降低(
P
<
0.01),结肠组织中MC密度明显升高(
P
<
0.05),血液以及结肠组织中的5-HT,SP,SS水平均明显增加(
P
<
0.05,
P
<
0.01),结肠组织中VIP表达明显提高(
P
<
0.05)。与模型组比较,戊己丸不同配伍方均可显著提高腹部抬起和弓背抬高阈值(
P
<
0.01),明显减少结肠组织MC数量(
P
<
0.05)及5-HT,SP,SS和VIP的表达(
P
<
0.05)。分析戊己丸不同配伍方作用得出,戊己丸1#方在降低血液中5-HT,SP及SS方面不同程度地强于2#方,其中尤以对5-HT的影响的差别最为显著(
P
<
0.01);而2#方在降低结肠5-HT阳性表达上与1#方差别无明显统计学意义,在下调SP阳性表达上显著优于1#方;对于结肠SS阳性表达,其阳性表达的强度及范围显著小于1#方(
P
<
0.05)。
结论
2
戊己丸不同配伍方均能调整IBS的胃肠激素紊乱,降低肠道敏感性;在整体作用上,1#方不同程度地强于2#方,而在肠道局部作用上,2#方显示出一定优势,而且1#方更长于对肠道动力学的影响,而2#方则对肠道感觉的影响更大一些。
Objective
2
To compare the therapeutic efficacies of Wujiwan at two different compatibilities (No.1 and No.2) on irritable bowel syndrome (IBS) based on neuro-endocrine-immune network, and provide a theoretical basis for the treatment based on syndrome differentiation in traditional Chinese medicine (TCM).
Method
2
The chronic animal model of IBS with visceral hypersensitivity was established by colon irritation via percutaneous transluminal coronary angioplasty (PTCA) in suckling rats. The animals were randomly divided into a control group, a model group, a dicetel group (0.01 g·kg
-1
), low- (0.335 g·kg
-
1
), medium- (0.67 g·kg
-
1
), and high-dose (1.34 g·kg
-
1
) No. 1 Wujiwan groups, and low- (0.385 g·kg
-
1
), medium- (0.77 g·kg
-
1
), and high-dose (1.54 g·kg
-
1
) No. 2 Wujiwan groups. The thresholds of abdominal elevation and bow back elevation were evaluated to detect the effect of Wujiwan on intestinal sensitivity of IBS. The density of mast cells (MC) in the colonic tissue of model rats was detected by the modified toluidine blue staining method. The concentrations/positive expression of 5-hydroxytryptamine (5-HT), substance P (SP), somatostatin (SS), and vasoactive intestinal peptide (VIP) in the blood/colon tissue were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assay.
Result
2
There was no significant difference in body weight among different groups. Compared with the control group, the model group exhibited decreased thresholds of abdominal elevation and bow back elevation (
P<
0.01), increased density of MCs in the colon tissue (
P<
0.05), up-regulated levels of 5-HT, SP, and SS in the blood and colon tissue (
P<
0.05,
P<
0.01), and elevated VIP level in the colon tissue (
P
<
0.05). Compared with the model group, Wujiwan at different compatibilities could increase the thresholds of abdominal elevation and bow back elevation (
P
<
0.01), diminish the count of MC in the colon tissue (
P
<
0.05), and reduce the levels of 5-HT, SP, SS, and VIP (
P
<
0.05). As demonstrated by the comparison of No. 1 and No. 2 Wujiwan, No. 1 was superior to No. 2 in reducing the concentrations of 5-HT, SP, and SS in the blood, especially in 5-HT (
P
<
0.01). No significant difference between No. 1 and No. 2 in reducing 5-HT positive expression in the colon tissue was observed. Compared to the No. 1 Wujiwan, No. 2 significantly reduced SP expression, and the intensity and range of SS expression in the colon tissue in the No. 2 groups were smaller than those in the No. 1 groups (
P
<
0.05).
Conclusion
2
Wujiwan at different compatibilities was capable of improving gastrointestinal hormone disorder of IBS to reduce intestinal sensitivity. In terms of systemic effect, No. 1 was superior to No. 2, while in terms of local effect, No. 2 was advantageous. No. 1 Wujiwan was superior to No. 2 in the effect on intestinal dynamics, while No. 2 had an advantageous effect on intestinal sensation over No. 1.
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