持续弹性外牵引对小型猪乳头及其支撑组织影响的实验研究
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摘要
目的：观察持续弹性外牵引对雌性小型猪乳头及其支撑组织的作用影响,了解上述组织在牵引过程中大体形态、组织病理及一些生长因子表达等方面的变化,从而以此探讨持续弹性外牵引技术矫正乳头内陷的作用机理,为更好的改进和利用该项技术矫正乳头内陷提供理论依据。方法：选用3月龄雌性小型猪3只,每只均有12个乳头,共计36个乳头。每只留取4个乳头作为空白对照,其余8个安放乳头内陷矫治器进行持续弹性外牵引,安放及后期乳头切取时均对小型猪施行肌肉注射氯胺酮8 mg/kg及速眠新Ⅱ注射液1.5ml的复合全身麻醉。。分别于牵引后2w、4w、8w、12w切取每只小型猪的1个空白乳头和2个牵引乳头,切除之前先用游标卡尺测量每个待切乳头的直径和高度,然后将切除的乳头标本分别行HE染色观察内部组织结构的变化,并计数镜下毛细血管数量；饱和苦味酸天狼星红染色观察组织中Ⅰ、Ⅲ型胶原分布及含量变化,结合图像分析软件进行定量分析；免疫组化染色观察血管内皮细胞生长因子(VEGF)、表皮细胞生长因子(EGF)以及CD34在组织中的表达情况,统计其阳性细胞的百分比及微血管密度(MVD)的变化。结果：大体形态上,牵引后乳头乳晕体积明显增大,乳头直径和高度同对照组相比均有显著差异(P<0.01),而且,乳头高度随牵引时间延长有逐渐增加的趋势,其中,8w、12w与2w,12w与4w相比有统计学意义(P<0.01或P<0.05)；普通光镜下观察HE染色组织,牵引组表皮增厚,基底细胞、成纤维细胞及毛细血管等增生明显,毛细血管计数与对照组比较有显著差异(P<0.01),其中,4w与12w相比亦有统计学意义(P<0.05)；饱和苦味酸天狼星红染色后,牵引组Ⅰ、Ⅲ型胶原含量及密度均有增加,同对照组相比,4w、8w、12w组Ⅰ型胶原有显著差异(P<0.01),2w、4w、8w、12w组Ⅲ型胶原有显著差异(P<0.01),Ⅰ/Ⅲ型胶原比值在牵引初期缩小,4w后逐渐增大,至12w时接近于正常对照组水平；免疫组化染色,各组乳头VEGF、CD34均有阳性表达,染色强度中等,对照组表达较弱,而EGF均为阴性表达。VEGF阳性表达的积分光密度值及MVD与对照组比较均有显著差异(P<0.01),二者之间呈显著正相关。结论：持续弹性外牵引促进小型猪乳头乳晕变化与临床乳头内陷患者乳头乳晕的变化过程大致相同,提示牵引对内陷乳头纠正的作用机理和对正常乳头的作用机理也大致相同。牵引后乳头乳晕增大的面积,除了有弹性伸展、机械蠕变和从周围移位而来的皮肤外,还有一部分为生物性增生的面积。牵引乳头的力量以维持弹簧有轻度张力不松弛即可,牵引时间以8w-12w为宜,可避免乳头内部组织的损伤,减少回缩发生。
Objective:to observe the effect of continuous elastic outside distraction on female minipig nipples and their supporting tissues, to comprehend the above-mentioned tissues'changes of general morphology, histopathology and expressions of some growth factors during the distraction process;thus,investigate the mechanism of continuous elastic outside distraction correcting inverted nipples, to improve this technique to correct inverted nipples and obtain better results.Methods:Three female 3 months old minipigs, which has 12 nipples, were employed.4 nipples of each minipig were remained without distraction were control group. And the other 8 nipples were continuously distracted with inverted nipple correction instruments which made by ourselves.The minipigs were employed generally anesthetized by intramuscular injection of ketamine (8 mg/kg) and SumianxinⅡinjection(1.5ml) for apply inverted nipple correction instruments and excising nipples.One nipple without distraction and two nipples distracted of each minipig were excised at 2,4,8 and 12 weeks after traction, respectively. Before excision, the diameters and heights of nipples were measured with a vernier caliper. Then the excised nipple specimens were employed HE staining for observation the change of their tissue structure and countting the numbers of capillaries.And employed saturated picric acid sirius red staining for observation distribution and content of typeⅠandⅢcollagen,and employed image analysis software for quantitative analysis. We observed the expressions of vascular endothelial cells growth factor (VEGF), epidermal growth factor (EGF), and CD34 in those tissues, counted percentage of positive cells and microvessel density (MVD) changes with immunohistochemical staining. Results: In general form, the volumes of nipples and areola papillaris all obviously increased after traction.compared with control group, diameters and heights of nipples are significantly different (p<0.01).In addition, there is a trend that following with traction time extension nipple height increase, in which 8w,12w groups compared with 2w and 12w compared with 4w groups all have obviously statistical significance (p<0.01 or p<0.05).Under ordinary light microscope, the traction group epidermis thickened, basal cells, fibroblasts and capillary significantly proliferated. Capillary counts compared with the control group were significantly different (p<0.01),which between 4w and 12w group have statistical significance(p<0.05).Stained with saturated picric acid sirius red,the typeⅠ、Ⅲcollagen contents of traction group all increased. Compared with control group, the typeⅠcollagen contents of 4w,8w,12w group were significantly different (p<0.05 or p<0.01),the typeⅢcollagen contents of 2w,4w,8w,12w group were significantly different (p<0.01),and the ratio ofⅠ/Ⅲreduced in the traction beginning, then gradually increased after 4w, to 12w is close to the ratio of control group.In immunohistochemical staining,VEGF、CD34 expressions of all groups were positive.The staining intensity of traction groups is moderate,and control groups were weakly positive.The EGF expression was all negative.The integral optical density of VEGF positive cell and MVD compared with the control group were significantly different (p<0.01),and there have a significant positive correlation in MVD and VEGF.Conclusion:continuous elastic outside distraction can promote female minipig nipple and areola papillaris to change,which is similar with the traction changes of clinical inverted nipple patients.These suggest that the action mechanism of traction for inverted nipples correction is same as the normal nipples. The increased areas of nipples and areola papillaris after traction are not come from flexible stretch, mechanical creep and shift of surrounding skins, but also partly from biological hyperplasia. The traction power can make spring maintain mild tension is enough and traction times of 8w to 12w are appropriate, which can avoid damage of inner tissues of nipples and reduce the occurrence of retraction.
Objective:to observe the effect of continuous elastic outside distraction on female minipig nipples and their supporting tissues, to comprehend the above-mentioned tissues'changes of general morphology, histopathology and expressions of some growth factors during the distraction process;thus,investigate the mechanism of continuous elastic outside distraction correcting inverted nipples, to improve this technique to correct inverted nipples and obtain better results.Methods:Three female 3 months old minipigs, which has 12 nipples, were employed.4 nipples of each minipig were remained without distraction were control group. And the other 8 nipples were continuously distracted with inverted nipple correction instruments which made by ourselves.The minipigs were employed generally anesthetized by intramuscular injection of ketamine (8 mg/kg) and SumianxinⅡinjection(1.5ml) for apply inverted nipple correction instruments and excising nipples.One nipple without distraction and two nipples distracted of each minipig were excised at 2,4,8 and 12 weeks after traction, respectively. Before excision, the diameters and heights of nipples were measured with a vernier caliper. Then the excised nipple specimens were employed HE staining for observation the change of their tissue structure and countting the numbers of capillaries.And employed saturated picric acid sirius red staining for observation distribution and content of typeⅠandⅢcollagen,and employed image analysis software for quantitative analysis. We observed the expressions of vascular endothelial cells growth factor (VEGF), epidermal growth factor (EGF), and CD34 in those tissues, counted percentage of positive cells and microvessel density (MVD) changes with immunohistochemical staining. Results: In general form, the volumes of nipples and areola papillaris all obviously increased after traction.compared with control group, diameters and heights of nipples are significantly different (p<0.01).In addition, there is a trend that following with traction time extension nipple height increase, in which 8w,12w groups compared with 2w and 12w compared with 4w groups all have obviously statistical significance (p<0.01 or p<0.05).Under ordinary light microscope, the traction group epidermis thickened, basal cells, fibroblasts and capillary significantly proliferated. Capillary counts compared with the control group were significantly different (p<0.01),which between 4w and 12w group have statistical significance(p<0.05).Stained with saturated picric acid sirius red,the typeⅠ、Ⅲcollagen contents of traction group all increased. Compared with control group, the typeⅠcollagen contents of 4w,8w,12w group were significantly different (p<0.05 or p<0.01),the typeⅢcollagen contents of 2w,4w,8w,12w group were significantly different (p<0.01),and the ratio ofⅠ/Ⅲreduced in the traction beginning, then gradually increased after 4w, to 12w is close to the ratio of control group.In immunohistochemical staining,VEGF、CD34 expressions of all groups were positive.The staining intensity of traction groups is moderate,and control groups were weakly positive.The EGF expression was all negative.The integral optical density of VEGF positive cell and MVD compared with the control group were significantly different (p<0.01),and there have a significant positive correlation in MVD and VEGF.Conclusion:continuous elastic outside distraction can promote female minipig nipple and areola papillaris to change,which is similar with the traction changes of clinical inverted nipple patients.These suggest that the action mechanism of traction for inverted nipples correction is same as the normal nipples. The increased areas of nipples and areola papillaris after traction are not come from flexible stretch, mechanical creep and shift of surrounding skins, but also partly from biological hyperplasia. The traction power can make spring maintain mild tension is enough and traction times of 8w to 12w are appropriate, which can avoid damage of inner tissues of nipples and reduce the occurrence of retraction.
引文
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