大黄黄连泻心汤、理中丸（汤）抗醋酸涂抹型胃溃疡药效学及作用机理的研究
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摘要
目的：大黄黄连泻心汤、理中丸(汤)均为临床常用的治疗消化系统疾患的经方，但两方所治病证有寒热之别。本文拟在有关大黄黄连泻心汤、理中丸(汤)古今文献研究、临床研究及药理研究基础上，从醋酸涂抹所致一胃溃疡模型大鼠入手，就两方的相关药效和机理进行深入系统探讨，以期明确主治病证寒热属性截然相反的两个方剂对同一个病证—醋酸涂抹所致胃溃疡的不同作用机理。
方法：Wistar大鼠随机分为空白对照组、假手术组、模型对照组、大黄黄连泻心汤组和理中丸(汤)组。采用醋酸涂抹法复制大鼠胃溃疡模型，手术后24h灌胃给药，对照组给予生理盐水，连续14d。
用游标卡尺测定通过溃疡中心的最大纵径和横径，用公式1计算溃疡面积大小，观察大黄黄连泻心汤、理中丸(汤)对醋酸涂抹法大鼠模型缩小溃疡面积的作用。
取血，离心得血清，检测醋酸涂抹所致胃溃疡模型大鼠血清一氧化氮(NO)、一氧化氮合成酶(iNOS)、内皮素(ET)、白细胞介素(IL-8)、肿瘤坏死因子-α(TNF-α)等项指标。
取相应胃组织，制备组织匀浆，检测胃组织超氧化物歧化酶(SOD)、丙二醛(MDA)、表皮生长因子(EGF)、转化生长因子(TGF-α)的含量变化。
结果：大黄黄连泻心汤、理中丸(汤)均可明显缩小醋酸涂抹所致胃溃疡模型大鼠的胃溃疡面积(与模型组相比均P＜0．01)。
大黄黄连泻心汤对醋酸涂抹法所致溃疡模型大鼠的SOD活性明显升高(与模型对照组比较，P＜0．01)，对MDA影响不显著；ET含量升高明显(与模型对照组比较，P＜0．01)；对NO、iNOS影响不明显；IL-8含量明显降低(与模型对照组比较，P＜0．01)，但TNF-α含量变化不明显；GAS含量明显降低(与模型对照组比较，P＜0．05)；可使醋酸涂抹所致溃疡大鼠模型EGF、TGF-α含量明显升高(与模型对照组比较，P＜0．01)。
理中丸(汤)对醋酸涂抹法所致溃疡模型大鼠的SOD活性明显升高、MDA含量明显降低(与模型对照组比较，均P＜0．01)；NO含量明显升高，而ET含量明显降低(与模型对照组比较，均P＜0．01)；GAS含量无明显影响；IL-8含量明显降低(与模型对照组比较，P＜0．05)，但TNF-α含量变化不明显；EGF、TGF-α含量明显升高(与模型对照组比较P＜0．05)。
结论：大黄黄连泻心汤与理中丸(汤)具有较好的抗醋酸涂抹所致模型大鼠胃溃疡的作用。
大黄黄连泻心汤抗溃疡机理与降低GAS、ET含量和增加EGF、TGF-α含量、抑制IL-8释放及提高SOD活性有关。
理中丸(汤)抗溃疡机理与增加NO含量、降低ET含量、调节NO／ET平衡和抑制IL-8释放、提高SOD活性、降低MDA含量及增加EGF、TGF-α含量有关。
大黄黄连泻心汤与理中丸(汤)属功用和主治病证之寒热属性截然相反的两首方剂，对同一消化性溃疡模型的作用机制不尽不同，为进一步通过不同功用属性之方剂指导建立相应属性模型的研究思路，提供了有益的部分对比实验依据。
Objective
Dahuanghuanglianxiexin Tang and Lizhong Wan(Tang) were classicalprescriptions in healing digestive system diseases, the former was used totreating heat sydrom, but the latter was opposite. Based on literature, clinicaland experimental research about the two prescriptions, we studied thephamacological effect and possible mechanisms of the two prescriptions inhealing acetic acid induced gastric ulcer in rats. The study aimed to determinethe different mechanisms on treatment to the same syndrome-gastric ulcercaused by acetic acid of the two prescriotions, which can treat syndromes ofdiametrically opposite properties of cold and heat.
Methods
1)50 Wistar rats were randomly divided into control group, sham-operatedgroup, model group, Dahuanghuanglianxiexin Tang group and LizhongWan(Tang) group. Gastric ulcer was induced by the glacial acetic acid method.Dahuanghuanglianxiexin Tang group and Lizhong Wan(Tang) group wereadministrated by gastric perfusion of the same volume ofDahuanghuanglianxiexin Tang and Lizhong Wan(Tang) once every day, andthe other three groups were given the same volume of normal saline onceevery day. All the groups were observed continuely 14 days.
2) The gross stucture of rat stomach was observed, the longest vertical andhorizontal diameters were measured by the vemier caliper and then calculatedthe ulcer area according to the fomula.
3) The rat blood was collected and centrifuged, and the obtained supematantwas serum. The content of NO, iNOS, ET, IL-8, TNF-αwas tested.
4) The stamoch tissue were taken and homogenated, the activity of SOD, thecontent of MDA, EGF, TGF-αwas tested.
Results
1)Effect of the two prescriptions therepy on the healing of gastric ulcerThe two prescriptions can shrink the size of ulcer area. There was asignificant difference between model group and the two treatment groups(P＜0.01).
2)Mechanism of Dahuanghuanglianxiexin Tang
The activity of SOD had been improved, which was significant differentbetween treatment group and model group(P＜0.01). But there was no obviouseffect on MDA.
The content of ET had been decreased, which was significantly differentfrommodel group, (P＜0.01), but the content of NO, iNOS had no obviouschanges.
The content of IL-8 had been decreased, which was significantly differentfrom model group, (P＜0.01). But there was no obvious effect on TNF-α.
The content of GAS had been decreased, which had significant difference withmodel group, (P＜0.05).
The content of EGF and TGF-αhad been increased, which were significantlydifferent from model group(P＜0.01).
3) Mechanism of Lizhong Wan(Tang)
The activity of SOD and the content of MDA had been both increased, andthere were significant difference between treatment group and modelgroup(P＜0.01).
The content of Nohad been increased and the content of ET had beendecreased, and there were significant difference between treatment group andmodel group(P＜0.01).
The content of IL-8 had been decreased, and there was obvious differencewith model group, (P＜0.05). But there was no obvious effect on TNF-α.
The content of EGF and TGF-αhad been increased, which were significantlydifferent from model group(P＜0.01).
Conclusions
1) The two prescriptions had good curative effect on gastric ulcer in rats.
2) The possible mechanism of Dahuanghuanglianxiexin Tang was that theprescription can reduce the content of GAS and ET, increase the content ofEGF, TGF-α, inhibit the release of IL-8 and improve the activity of SOD.
3) The possible mechanism of Lizhong Wan(Tang) was that the prescriptioncan increase the content of NO, decrease the content of ET, and then revertNO/ET to the balance condition, inhibit the release of IL-8, improve theactivity of SOD, and at the same time reduce the content of MDA, increase the content of EGF, TGF-α.
3) Dahuanghuanglianxiexin Tang treated heat syndrome of gastric ulcer, whileLizhong Wan(Tang) treated cold syndrome of gastric ulcer. Although they hadsame therepeutic effects on the same gastric ulcer in model rats, themechanisms of those two prescriptions were different.
The results proved that it was proper and necessary of sydrome differentiation,and treatment correspondence between prescriptions and sydromes. And theresults also provided the experimental evidences and data for the clinicalapplication of the two classical prescriptions.
方法：Wistar大鼠随机分为空白对照组、假手术组、模型对照组、大黄黄连泻心汤组和理中丸(汤)组。采用醋酸涂抹法复制大鼠胃溃疡模型，手术后24h灌胃给药，对照组给予生理盐水，连续14d。
用游标卡尺测定通过溃疡中心的最大纵径和横径，用公式1计算溃疡面积大小，观察大黄黄连泻心汤、理中丸(汤)对醋酸涂抹法大鼠模型缩小溃疡面积的作用。
取血，离心得血清，检测醋酸涂抹所致胃溃疡模型大鼠血清一氧化氮(NO)、一氧化氮合成酶(iNOS)、内皮素(ET)、白细胞介素(IL-8)、肿瘤坏死因子-α(TNF-α)等项指标。
取相应胃组织，制备组织匀浆，检测胃组织超氧化物歧化酶(SOD)、丙二醛(MDA)、表皮生长因子(EGF)、转化生长因子(TGF-α)的含量变化。
结果：大黄黄连泻心汤、理中丸(汤)均可明显缩小醋酸涂抹所致胃溃疡模型大鼠的胃溃疡面积(与模型组相比均P＜0．01)。
大黄黄连泻心汤对醋酸涂抹法所致溃疡模型大鼠的SOD活性明显升高(与模型对照组比较，P＜0．01)，对MDA影响不显著；ET含量升高明显(与模型对照组比较，P＜0．01)；对NO、iNOS影响不明显；IL-8含量明显降低(与模型对照组比较，P＜0．01)，但TNF-α含量变化不明显；GAS含量明显降低(与模型对照组比较，P＜0．05)；可使醋酸涂抹所致溃疡大鼠模型EGF、TGF-α含量明显升高(与模型对照组比较，P＜0．01)。
理中丸(汤)对醋酸涂抹法所致溃疡模型大鼠的SOD活性明显升高、MDA含量明显降低(与模型对照组比较，均P＜0．01)；NO含量明显升高，而ET含量明显降低(与模型对照组比较，均P＜0．01)；GAS含量无明显影响；IL-8含量明显降低(与模型对照组比较，P＜0．05)，但TNF-α含量变化不明显；EGF、TGF-α含量明显升高(与模型对照组比较P＜0．05)。
结论：大黄黄连泻心汤与理中丸(汤)具有较好的抗醋酸涂抹所致模型大鼠胃溃疡的作用。
大黄黄连泻心汤抗溃疡机理与降低GAS、ET含量和增加EGF、TGF-α含量、抑制IL-8释放及提高SOD活性有关。
理中丸(汤)抗溃疡机理与增加NO含量、降低ET含量、调节NO／ET平衡和抑制IL-8释放、提高SOD活性、降低MDA含量及增加EGF、TGF-α含量有关。
大黄黄连泻心汤与理中丸(汤)属功用和主治病证之寒热属性截然相反的两首方剂，对同一消化性溃疡模型的作用机制不尽不同，为进一步通过不同功用属性之方剂指导建立相应属性模型的研究思路，提供了有益的部分对比实验依据。
Objective
Dahuanghuanglianxiexin Tang and Lizhong Wan(Tang) were classicalprescriptions in healing digestive system diseases, the former was used totreating heat sydrom, but the latter was opposite. Based on literature, clinicaland experimental research about the two prescriptions, we studied thephamacological effect and possible mechanisms of the two prescriptions inhealing acetic acid induced gastric ulcer in rats. The study aimed to determinethe different mechanisms on treatment to the same syndrome-gastric ulcercaused by acetic acid of the two prescriotions, which can treat syndromes ofdiametrically opposite properties of cold and heat.
Methods
1)50 Wistar rats were randomly divided into control group, sham-operatedgroup, model group, Dahuanghuanglianxiexin Tang group and LizhongWan(Tang) group. Gastric ulcer was induced by the glacial acetic acid method.Dahuanghuanglianxiexin Tang group and Lizhong Wan(Tang) group wereadministrated by gastric perfusion of the same volume ofDahuanghuanglianxiexin Tang and Lizhong Wan(Tang) once every day, andthe other three groups were given the same volume of normal saline onceevery day. All the groups were observed continuely 14 days.
2) The gross stucture of rat stomach was observed, the longest vertical andhorizontal diameters were measured by the vemier caliper and then calculatedthe ulcer area according to the fomula.
3) The rat blood was collected and centrifuged, and the obtained supematantwas serum. The content of NO, iNOS, ET, IL-8, TNF-αwas tested.
4) The stamoch tissue were taken and homogenated, the activity of SOD, thecontent of MDA, EGF, TGF-αwas tested.
Results
1)Effect of the two prescriptions therepy on the healing of gastric ulcerThe two prescriptions can shrink the size of ulcer area. There was asignificant difference between model group and the two treatment groups(P＜0.01).
2)Mechanism of Dahuanghuanglianxiexin Tang
The activity of SOD had been improved, which was significant differentbetween treatment group and model group(P＜0.01). But there was no obviouseffect on MDA.
The content of ET had been decreased, which was significantly differentfrommodel group, (P＜0.01), but the content of NO, iNOS had no obviouschanges.
The content of IL-8 had been decreased, which was significantly differentfrom model group, (P＜0.01). But there was no obvious effect on TNF-α.
The content of GAS had been decreased, which had significant difference withmodel group, (P＜0.05).
The content of EGF and TGF-αhad been increased, which were significantlydifferent from model group(P＜0.01).
3) Mechanism of Lizhong Wan(Tang)
The activity of SOD and the content of MDA had been both increased, andthere were significant difference between treatment group and modelgroup(P＜0.01).
The content of Nohad been increased and the content of ET had beendecreased, and there were significant difference between treatment group andmodel group(P＜0.01).
The content of IL-8 had been decreased, and there was obvious differencewith model group, (P＜0.05). But there was no obvious effect on TNF-α.
The content of EGF and TGF-αhad been increased, which were significantlydifferent from model group(P＜0.01).
Conclusions
1) The two prescriptions had good curative effect on gastric ulcer in rats.
2) The possible mechanism of Dahuanghuanglianxiexin Tang was that theprescription can reduce the content of GAS and ET, increase the content ofEGF, TGF-α, inhibit the release of IL-8 and improve the activity of SOD.
3) The possible mechanism of Lizhong Wan(Tang) was that the prescriptioncan increase the content of NO, decrease the content of ET, and then revertNO/ET to the balance condition, inhibit the release of IL-8, improve theactivity of SOD, and at the same time reduce the content of MDA, increase the content of EGF, TGF-α.
3) Dahuanghuanglianxiexin Tang treated heat syndrome of gastric ulcer, whileLizhong Wan(Tang) treated cold syndrome of gastric ulcer. Although they hadsame therepeutic effects on the same gastric ulcer in model rats, themechanisms of those two prescriptions were different.
The results proved that it was proper and necessary of sydrome differentiation,and treatment correspondence between prescriptions and sydromes. And theresults also provided the experimental evidences and data for the clinicalapplication of the two classical prescriptions.
引文
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