宫环止血片对置CU-IUD家兔子宫内膜TNF-a、IL-2含量及iNOS表达的影响
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摘要
目的：宫环止血片系我院妇科专家尤昭玲教授根据多年的临床经验总结所创,临床应用疗效显著。本课题以中医药理论为指导,采用现代科学试验研究手段,在以前的试验基础上,探讨宫环止血片对置铜宫内节育器(Cu-IUD)家兔子宫内膜局部TNF-α、IL-2含量及诱生型二氧化氮合酶(Inos)蛋白表达的影响。
方法：将家兔随机分为7组：空白组、假手术组、模型组、吲哚美辛组、宫环止血片大剂量组、宫环止血片中剂量组和宫环止血片小剂量组。建立置Cu-IUD家兔的动物模型,用吲哚美辛作对照,采用放射免疫法对各组家兔子宫匀浆液TNF-a和IL-2的含量进行测定,对各组家兔子宫内膜进行免疫组织化学染色,应用图像分析法检测宫环止血片对置Cu-IUD家兔子宫内膜iNOS蛋白的表达水平。
结果：模型组家兔子宫内膜iNOS蛋白表达的平均面积、平均光密度、阳性细胞数明显高于空白对照组,平均灰度值明显低于空白对照组,差异具有显著性意义(P<0.01)。说明模型组家兔子宫内膜iNOS蛋白表达较空白对照组明显增高。
宫环止血片大、中、小剂量组与模型组比较,子宫内膜iNOS蛋白表达的平均面积、平均光密度、阳性细胞数明显低于模型组,平均灰度值明显高于模型组,差异具有显著性意义(P<0.01)。说明经宫环止血片治疗后家兔子宫内膜iNOS蛋白表达明显降低。
模型组家兔子宫匀浆液TNF-a含量较空白对照组明显增高,IL-2含量明显降低,差异具有显著性意义(P<0.01),经宫环止血片治疗后家兔子宫匀浆液中TNF-a含量明显降低(宫环止血片大、中、小剂量组与模型组比较P<0.01)IL-2含量明显增(宫环止血片大、中、小剂量组与模型组比较P<0.01)。
结论：上述试验结果表明：CU-IUD对子宫内膜产生局部机械压迫,引起内膜充血、坏死,表浅溃疡形成而不易愈合,iNOS被大量诱导产生,生成大量NO,可能是其导致子宫内膜异常出血的又一机制。而宫环止血片可以明显降低子宫内膜中iNOS蛋白的表达水平,调节血管的收缩功能,而使子宫异常出血减少,宫环止血片还可通过降低置Cu-IUD家兔子宫匀浆液中TNF-a含量,增高IL-2含量使免疫机能增强,提示宫环止血片能减轻置器后子宫局部坏死及无菌性炎症,有效地提高机体免疫机能,增强抗感染能力。
本实验证实,宫环止血片可以明显降低子宫内膜中iNOS蛋白的表达水平,降低子宫匀浆液中TNF-a含量,增高IL-2含量,为防治IUD引起子宫异常出血的药理机制提供新的理论依据,也证明本方通过多重机制起作用,同时证实中药复方多途径,多靶点作用的一般规律。为中医药防治IUD引起异常出血的研究开拓新的思路和着眼点。
Objective:Gonghuanzhixue tablets has predominant therapeutic effect in clinic, which was created by You Zhaoling, the specialist of department of gynecology, according to many years' clinical experience. This topic was guided by traditional Chinese medicine and was adopted modern scientific experiments.In the former experiment bases, to explore the effect of Gonghuanzhixue tablets on the content of TNF-a,IL-2 and the express of iNOS in endometria of CU-IUD-wearing rabbits.
Methods:The rabbits were divided into blank group, sham operation group, model group, indomethacin group, high-dose-group, middle-dose-group and low-dose group.The animal model of CU-IUD-wearing rabbits was established.Compared with indomethacin, to determine the content of TNF-a and IL-2 of homogenate by radioimmunity.The immunohistochemistry dyeing was used in the endometria of rabbits in every group. To detect the express level of Gonghuanzhixue tablets on the protein of iNOS in endometria by image analysis.
Result:The surface density,average optical and masculine cell population expressed by iNOS in the model group were more than those of blank group, but the average gray scale was lower than these of blank group. There were significant differences between the two groups(P<0.01). They could explain that the express of iNOS in model group was higher than those in the blank group.
Compared to model group, the surface density, average optical and masculine cell population expressed by iNOS was low in the high-dose-group, middle-dose-group and low-dose group but the average gray scale was high.There were significant differences between the two groups (P<0.01).They could explain that the express of iNOS in endometria depressed obviously after treatmented by Gonghuanzhixue tablets.
Compared to control group, the content of TNF-a in homogenate was high in model group and the content of IL-2 depressed.There were significant differences between the two groups (P<0.01).After treatmented by Gonghuanzhixue tablets, the content of TNF-a in homogenate depressed obviously (the content of TNF-a in high-dose-group,middle-dose-group and low-dose group was different from those of model group, P<0.01), the content of IL-2 in homogenate increased obviously (the content of IL-2 in high-dose-group, middle-dose-group and low-dose group was different from those of model group, P<0.01).
Conclusion:The result of the experiment indicated that:CU-IUD could form mechanical pressure for iNOS.It could cause congestion, cellular necrosis and superficial anabrosis of endometrium. The production of iNOS was induced and much NO formed.These may be another mechanism for abnormal bleeding.Gonghuanzhixue tablets could depress the express level of iNOS in endometrium, adjust the contractile function of blood vessel, so reduced the abnormal bleeding of hystera. It could also increase the content of IL-2 and enhance the immune function by decreasing the content of TNF-a of homogenate. These indicated that Gonghuanzhixue tablets could enhance the immune function and anti-infection.
The experiment confirmed that Gonghuanzhixue tablets could decrease the express level of iNOS, the content of TNF-a in endometrium, but could increase the content of IL-2. It provided new theory base for the mechanism of preventing and curing abnormal bleeding according by IUD.It also confirmed that Gonghuanzhixue tablets reacted by multiplicitas mechanism and effected by many paths and many targets. And this would improve new methods for preventing and curing abnormal bleeding caused by IUD.
方法：将家兔随机分为7组：空白组、假手术组、模型组、吲哚美辛组、宫环止血片大剂量组、宫环止血片中剂量组和宫环止血片小剂量组。建立置Cu-IUD家兔的动物模型,用吲哚美辛作对照,采用放射免疫法对各组家兔子宫匀浆液TNF-a和IL-2的含量进行测定,对各组家兔子宫内膜进行免疫组织化学染色,应用图像分析法检测宫环止血片对置Cu-IUD家兔子宫内膜iNOS蛋白的表达水平。
结果：模型组家兔子宫内膜iNOS蛋白表达的平均面积、平均光密度、阳性细胞数明显高于空白对照组,平均灰度值明显低于空白对照组,差异具有显著性意义(P<0.01)。说明模型组家兔子宫内膜iNOS蛋白表达较空白对照组明显增高。
宫环止血片大、中、小剂量组与模型组比较,子宫内膜iNOS蛋白表达的平均面积、平均光密度、阳性细胞数明显低于模型组,平均灰度值明显高于模型组,差异具有显著性意义(P<0.01)。说明经宫环止血片治疗后家兔子宫内膜iNOS蛋白表达明显降低。
模型组家兔子宫匀浆液TNF-a含量较空白对照组明显增高,IL-2含量明显降低,差异具有显著性意义(P<0.01),经宫环止血片治疗后家兔子宫匀浆液中TNF-a含量明显降低(宫环止血片大、中、小剂量组与模型组比较P<0.01)IL-2含量明显增(宫环止血片大、中、小剂量组与模型组比较P<0.01)。
结论：上述试验结果表明：CU-IUD对子宫内膜产生局部机械压迫,引起内膜充血、坏死,表浅溃疡形成而不易愈合,iNOS被大量诱导产生,生成大量NO,可能是其导致子宫内膜异常出血的又一机制。而宫环止血片可以明显降低子宫内膜中iNOS蛋白的表达水平,调节血管的收缩功能,而使子宫异常出血减少,宫环止血片还可通过降低置Cu-IUD家兔子宫匀浆液中TNF-a含量,增高IL-2含量使免疫机能增强,提示宫环止血片能减轻置器后子宫局部坏死及无菌性炎症,有效地提高机体免疫机能,增强抗感染能力。
本实验证实,宫环止血片可以明显降低子宫内膜中iNOS蛋白的表达水平,降低子宫匀浆液中TNF-a含量,增高IL-2含量,为防治IUD引起子宫异常出血的药理机制提供新的理论依据,也证明本方通过多重机制起作用,同时证实中药复方多途径,多靶点作用的一般规律。为中医药防治IUD引起异常出血的研究开拓新的思路和着眼点。
Objective:Gonghuanzhixue tablets has predominant therapeutic effect in clinic, which was created by You Zhaoling, the specialist of department of gynecology, according to many years' clinical experience. This topic was guided by traditional Chinese medicine and was adopted modern scientific experiments.In the former experiment bases, to explore the effect of Gonghuanzhixue tablets on the content of TNF-a,IL-2 and the express of iNOS in endometria of CU-IUD-wearing rabbits.
Methods:The rabbits were divided into blank group, sham operation group, model group, indomethacin group, high-dose-group, middle-dose-group and low-dose group.The animal model of CU-IUD-wearing rabbits was established.Compared with indomethacin, to determine the content of TNF-a and IL-2 of homogenate by radioimmunity.The immunohistochemistry dyeing was used in the endometria of rabbits in every group. To detect the express level of Gonghuanzhixue tablets on the protein of iNOS in endometria by image analysis.
Result:The surface density,average optical and masculine cell population expressed by iNOS in the model group were more than those of blank group, but the average gray scale was lower than these of blank group. There were significant differences between the two groups(P<0.01). They could explain that the express of iNOS in model group was higher than those in the blank group.
Compared to model group, the surface density, average optical and masculine cell population expressed by iNOS was low in the high-dose-group, middle-dose-group and low-dose group but the average gray scale was high.There were significant differences between the two groups (P<0.01).They could explain that the express of iNOS in endometria depressed obviously after treatmented by Gonghuanzhixue tablets.
Compared to control group, the content of TNF-a in homogenate was high in model group and the content of IL-2 depressed.There were significant differences between the two groups (P<0.01).After treatmented by Gonghuanzhixue tablets, the content of TNF-a in homogenate depressed obviously (the content of TNF-a in high-dose-group,middle-dose-group and low-dose group was different from those of model group, P<0.01), the content of IL-2 in homogenate increased obviously (the content of IL-2 in high-dose-group, middle-dose-group and low-dose group was different from those of model group, P<0.01).
Conclusion:The result of the experiment indicated that:CU-IUD could form mechanical pressure for iNOS.It could cause congestion, cellular necrosis and superficial anabrosis of endometrium. The production of iNOS was induced and much NO formed.These may be another mechanism for abnormal bleeding.Gonghuanzhixue tablets could depress the express level of iNOS in endometrium, adjust the contractile function of blood vessel, so reduced the abnormal bleeding of hystera. It could also increase the content of IL-2 and enhance the immune function by decreasing the content of TNF-a of homogenate. These indicated that Gonghuanzhixue tablets could enhance the immune function and anti-infection.
The experiment confirmed that Gonghuanzhixue tablets could decrease the express level of iNOS, the content of TNF-a in endometrium, but could increase the content of IL-2. It provided new theory base for the mechanism of preventing and curing abnormal bleeding according by IUD.It also confirmed that Gonghuanzhixue tablets reacted by multiplicitas mechanism and effected by many paths and many targets. And this would improve new methods for preventing and curing abnormal bleeding caused by IUD.
引文
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