【作者】 胡艳；

【导师】 陈锐深；

【作者基本信息】 广州中医药大学 ， 中西医结合临床， 2009， 博士

【摘要】 第一章文献研究与立论依据论述了祖国医学对放射所致皮肤损伤的研究分析、现代医学对于放疗所致皮肤损伤的的研究分析以及本项研究的立论依据与研究意义。第二章临床研究目的:客观评价中药金虎膏防治头颈部恶性肿瘤放疗所致皮肤损伤的疗效,探讨放射性皮炎的有效治疗方案。方法:将60例需要进行放射治疗的头颈部恶性肿瘤患者随机分为治疗组和对照组,其中治疗组病例30例,对照组病例30例,治疗组在第1次放疗结束后外敷金虎膏至放疗疗程结束,对照组照射野皮肤未予特殊处理,比较两组在放射治疗过程中放射性皮炎的发生率、放射性皮炎分级、放射性皮炎皮肤反应发生的放射剂量及药物不良反应等。结果:两组患者皮肤反应发生率为100%,但皮肷反应发生的严重程度上,治疗组严重程度显著低于对照组(P＜0.05);轻度放射反应(Ⅰ级+Ⅱ级)疗组为70.0%,对照组为40.0%,有显著性差异(P＜0.05);中重度放射反应(Ⅲ级)治疗组30.0%,对照组为60.0%,两组对比有显著性差异(P＜0.05),说明金虎膏能在一定程度上顶防中重度皮肤反应的发生;皮肤放射性反应治疗组26.7%(8例)出现于照射40 Gy以前,对照组60.0%(13例)出现于照射40Gy以前,两组统计上有显著性差异(P＜0.05),治疗组83.3%(22例)出现于照射40 Gy以后,对照组40.0%(22例)出现于照射40Gy以后,两组统计上有显著性差异(P＜0.05),说明通常在放疗中后期剂量达到40Gy后放射性皮炎发生明显,尤其是在60～70Gy剂量达到高峰;当患者皮肽损伤出现创面后,经继续给药治疗后治疗组创面新生皮肤粘膜修复平均天数为7.31天,对照组为9.68天,经统计学分析,有显著性差异(P＜0.05)。放射治疗后患者的生存质量以稳定和降低为主,治疗组与对照组相比无显著性差异化(P＞0.05)。两组患者在治疗中均未出现任何急性、毒性等不良反应。结论:金虎膏能有效地预防放射性皮炎的发生,加速创面的愈合,对患者能减轻痛苦、提高生活质量、减轻放射治疗副反应,保证放射治疗的顺利进行。临床应用中金虎膏治疗组未见任何毒副反应的发生。第三章实验研究目的:客观评价中药金虎膏防治头颈部恶性肿瘤放疗所致皮肤损伤的疗效,探讨放射性皮炎的有效治疗方案。方法:将40只雌性SD大鼠用硫化钡进行左后肢照射野脱毛并麻醉,将其固定在自制大鼠台上,照射面积为2.0×2.0cm,身体其他部分用铅板屏蔽,以瑞典医科达直线加速器电子线6MeV单次照射,剂量率为200cGy/min,吸收剂量为40Gy。照射后送回动物室随机分为4组,治疗组、对照组、模型组和正常组,每组10只。治疗组大鼠左后肢皮肤予以生理盐水清创后,外涂金虎膏;对照组大鼠左后肢皮肤予以生理盐水清创后,外涂比亚芬;模型组大鼠左后肢皮肤单纯予以生理盐水清创,均每日1次,给药30天,正常组大鼠不予以造模及给药。观察创面出现及愈合的时间;光镜和电镜观察创面愈合过程中组织学改变;RT-PCR法检测创面愈合过程中Ku70和Ku80mRNA表达变化。结果:两组大鼠皮肤反应发生率为100%,说明放射性皮炎动物模型成功。但皮肤反应发生的严重程度上,三组相比较,统计学上无显著性差异(P＞0.05),但模型组出现Ⅳ级放射性皮炎反应2例,对照组出现1例,治疗组严重程度低于模型组,说明金虎膏能在一定程度上预防放射性皮肤反应的发生。光镜下观察发现发现照射14天,三组没有明显病理变化差异;照射30天后,治疗组与对照组均可见部分修复创面,纤维母细胞、胶原纤维增生,而模型组创面皮损明显,表皮与真皮层组织坏死明显,大量炎细胞浸润,说明金虎膏与比亚芬均能加速创面的修复,促进伤口愈合。电镜对其超微结构的变化观察发现,照射14天后治疗组成纤维细胞内线粒体嵴变短减少,个别线粒体轻微空化,内质网轻度扩张,照射30天后治疗组毛囊基本消失,真皮层中结缔组织和胶原纤维增生,达到愈合;三组比较发现皮肤出现放射性损伤后,毛囊基本消失,真皮层中结缔组织和胶原纤维增生,这说明金虎膏能够对损伤皮肤进行修复,促进胶原蛋白合成,从而使伤口结痂愈合。通过实时荧光定量PCR对Ku70/Ku80 mRNA在不同组别的表达差异测定发现,照射14天后,治疗组、对照组Ku70 mRNA的表达均高于正常组,无显著性差异(P＞0.05),模型组Ku70 mRNA的表达低于正常组,无显著性差异(P＞0.05);治疗组、对照组Ku70 mRNA的表达均高于模型组,有显著性差异(P＜0.05)。照射30天后,治疗组、对照组、模型组Ku70 mRNA的表达均高于正常组,经统计学分析,有显著性差异(P＜0.05),其中治疗组和对照组与模型组比较,有显著性差异(P＜0.05),治疗组与对照组比较,无显著性差异(P＞0.05)。表明经过放射后皮肤组织中Ku70mRNA表达减少,通过药物对其组织的修复能够提高表达量。照射14天后,治疗组、对照组、模型组Ku80 mRNA的表达均低于正常组,经统计学分析,有显著性差异(P＜0.05),其中治疗组和对照组与模型组比较,无显著性差异(P＞0.05);照射30天后,治疗组、对照组、模型组Ku80 mRNA的表达仍低于正常组,经统计学分析,有显著性差异(P＜0.05),其中治疗组和对照组与模型组比较,有显著性差异(P＜0.05),治疗组与对照组比较,无显著性差异(p＞0.O5)。表明Ku80mRNA在正常组织中表达较高,经过放射后皮肤组织中表达明显减少,但是通过金虎膏、比亚芬等药物治疗能提高其表达。结论:金虎膏在高能电子线造成的皮肤损伤创面愈合过程中起重要作用,促进胶原蛋白合成,可促进Ku70/Ku80的表达与合成,从而促进创面愈合。并对大鼠完整皮肤和破损皮肤均不产生任何急性毒性反应。更多还原

【Abstract】 PartⅠLiterature Review and StudyWe studied the knowledge of Modern Medicine and Traditional Chinese Medicine(TCM) to radiodermatitis.Then We discussed the basic and significance of the research.PartⅡClinical StudyObjective:To obsever the therapeutic efficacy of Jinhu Cream in preventing and treating acute radiodermatitisMethods:60 patients with Head and Neck Cancers were divided randomly into two groups.In Group A(as a treatment group),30 patients were treated with Jinhu Cream since the first radiotherapy session.In Group B(as a control group),30 patients were given general and health education since the first radiotherapy session.The therapeutic efficancy of the two groups were evaluated after two course of treatment.Results:The rate of the skin-reaction was 100%in the patients of both groups. A mild radiation reaction(gradeⅠandⅡ) occurred as follows: 70.0%(21/30cases) in Group A and 40.0%(12/30 cases) in Group B.A severe reaction(grade-Ⅲ) radiation reaction developed in 30.0%in Group A,and 60.0%in GroupB.There was a significant difference(P<0.05) between the two groups.Concerning the degree of the skin response before the patients received a dose of 40 Gy,the radiation reaction emerged in 26.7%of the cases in Group A,and in 60%of the cases of Group B.The mean time for curing radioactive dermatitis,Group A and B was 7.31 and 9.68 days.There was a significant difference(P<0.05) between the two groups.Group A had the same quality of life with Group B.Jinhu Cream had no severe adverse reaction.Conclusion:Jinhu Cream can effectively prevent acute irradiator induced dermal injury.It can alleviate the patients’ suffering and improve the quality of life,so as to ensure uneventful radiotherapy.PartⅢAnimal ExperimentObjective:By the animal experiment,to observe the curative effect of Jinhu Cream on on skin ulcer induced by radiation in rats and the expressions of Ku70/Ku80 mRNA in acute irradiated skin injury in rats,the result of which would be based for further clinical research.Methods:In this model the radiation injury on hip skin of female SD rats was induced by 6MeV electrons from an electron linear accelerator.Experimental animals were divided into 4 groups,Group A(the model group treated with Sodium Chloride),Group B(the control group treated with Biafine cream) and Group C(treated with Jinhu cream) and Group D(the blank group).After treated with 14 and 30 days,the pathological changes was observed macroscopically and by light and electron microscopy.The irradiated skins of the rats were examined by real-time quantitative PCR to detect the expressions of Ku70/Ku80 mRNA.Results:The rate of the skin-reaction was 100%in rats of both groups.There was no significant difference(P>0.05) between three groups.The morphologic changes of Group A,B,C wasn’ t obviously under light microscope after 14 days. There was significant difference in the pathological changes after 30 days. It could observe part of wound repair,the proliferation of fibroblasts and collagen fiber in Group B and C whlie obviously wound lesions,epidermis and dermis tissue necrosis,a large number of inflammatory cell infiltration in Group A.Under electron microscope,the swelling of mitochondria and endoplasmic reticulum,apoptosis in basal cells,swelling,pyknosis,cavity narrowing and thrombosis in microvessels,disruption of collagenous fibrils and apotosis in fibroblasts can be observed in Group A,B,and C after 30 days. The contents of Ku70 mRNA in the skin of Group C were significantly decreased than that in Group A(P<0.05) after 30 days.The contents of Ku80 mRNA in the skin of Group C were significantly increased than that in Group A(P< 0.05) after 30 days.Conclusion:Jinhu Cream can effectively cure radiation skin ulcer,and the effect is especially significant on the ulcer induced.It can promote the composition of collagen and increase the expressions of Ku70/Ku80 mRNA,then improve wound healing.And integrity of the skin and damaged skin of the rats did not have acute toxicity.更多还原