【作者】 肖敏；

【导师】 艾儒棣；

【作者基本信息】 成都中医药大学 ， 中医外科学， 2013， 博士

【摘要】 目的：皮肤慢性溃疡是临床常见的难治性疾病,病程迁延反复,给患者带来巨大的生理和心理痛苦,目前其愈合机制尚未完全清楚,治疗也颇为棘手。本研究旨在通过皮肤慢性溃疡的实验室与临床研究,从分子生物学水平探索皮肤慢性溃疡的愈合机制,进一步探求中药治疗该病的作用靶点,用客观的数据证实蜚蠊提取液治疗皮肤慢性溃疡的有效性,为寻求有效、方便、价廉的治疗方案提供实验室依据和研究数据支持。方法：把符合纳入标准的皮肤慢性溃疡患者68人随机分为治疗组33人,对照组35人。如有合感染的病人可全身抗感染治疗,如合并糖尿病患者可以同时采用降糖药物。二组均用生理盐水棉球将创面清洗干净,用干棉球拭干,治疗组用蜚蠊提取液(康复新液)湿敷,对照组将生肌散“飞”到溃疡面上,然后用无菌纱布包扎。二组均每日更换敷料1次,治疗4周。观察皮损愈合情况和治愈率。治疗前后取皮损病理切片,用免疫组化法检测皮损的Smad3基因表达水平、TGF-01和VEGF表达水平。结果：治疗前,试验组和对照组皮损面积、溃疡色泽积分、分泌物积分、自觉疼痛程度积分、皮损的气味积分、空腹血糖水平组间对比无明显差异(P>0.05),具有可比性；治疗1、2、3、4周后,试验组与对照组皮损面积无明显差异(P>0.05)；试验组和对照组病例溃疡面分泌物积分均无明显差异(P>0.05)；试验组和对照组病例溃疡面气味积分均无明显差异(P>0.05)；试验组病例空腹血糖水平低于6.1mmol/L、6.1～11.1mmol/L.高于11.1mmol/L的例数分别是21例、8例、5例,对照组分别是23例、6例、5例,试验组和对照组空腹血糖水平分组对照无明显差异,(P<0.05)；试验组痊愈率、显效率、好转率和无效率分别是分别是8.82%、29.41%、47.06%、14.71%,对照组的痊愈率、显效率、好转率和无效率分别是14.71%、26.47%、47.06%、11.76%,治疗4周后,试验组患者痊愈率明显低于对照组,(P<0.05),显效率、好转率和无效率均无明显差异,具有可比性,(P>0.05)；治疗第1周和第2周,试验组和对照组病例溃疡色泽积分无明显差异(P>0.05),治疗第3周和第4周,试验组病例溃疡色泽积分明显低于对照组,(P<0.05),治疗1周、2周、3周后,试验组和对照组病例自觉疼痛程度无明显差异(P>0.05),治疗4周后,试验组病例自觉疼痛程度明显小于对照组(P<0.05)；试验组病例中长期卧床或行动受限者、伴发糖尿病者、伴发静脉曲张者、外伤诱发者、放射线照射者分别是3例、13例、17例、21例、2例,试验组分别是4例、11例、18例、25例、2例,试验组和对照组组间数据对比无显著差异,具有可比性,(P>0.05)；试验组病例中出现用药后疼痛、瘙痒者分别是1例、2例,对照组分别是2例、2例；试验组和对照组病例中,以41-50岁和51～60岁的最多,一共占到总例数的60%左右。治疗前,实验组Smad3基因、TGF-β1、VEGF表达阳性细胞数比例是79.62±5.26%、29.74±3.12%、21.65±3.12%,对照组阳性细胞数比例分别是78.32±4.97%、29.13±3.98%、22.44±3.11%,治疗4周后,实验组Smad3基因、TGF-β1、VEGF表达阳性细胞数比例分别是18.85±1.88%、79.07±7.80%、59.24±3.74%；对照组阳性细胞数比例分别是20.03±2.42%、77.47±7.68%、61.09±4.10%,实验组和对照组皮损病理切片Smad3基因、TGF-β1、VEGF表达水平无明显差异,具有可比性(P>0.05)；治疗4周后,实验组切片Smad3基因表达水平低于对照组,TGF-β1、VEGF表达阳性细胞数比例高于对照组,但是不具有统计学意义(P>0.05)；治疗前后对照,实验组Smad3基因表达水平显著下降,(P<0.05),TGF-β1、UVEGF表达水平明显升高(P<0.05)。结论：1.蜚蠊提取液有促进创面愈合的作用,临床疗效与对照组相当。治疗后试验组和对照组的皮损面积,分泌物积分,气味积分,显效率、好转率和无效率没有明显差异；试验组皮损色泽积分、自觉疼痛程度积分、痊愈率三项指标临床疗效优于对照组；试验组和对照组分别有3例、4例病例出现用药后疼痛、瘙痒；试验组和对照组病例中,以41-50岁和51-60岁的最多,一共占到总例数的60%左右；蜚蠊提取液用于治疗皮肤慢性溃疡具有有效性、安全性。2.蜚蠊提取液可能是通过下调Smad3基因表达水平,同时TGF-β1、VEGF的生成和游走,促进创面毛细血管再生、肉芽组织新生,从而加快皮肤慢性溃疡创面愈合。更多还原

【Abstract】 Objective:chronic skin ulcer is a common. refractory disease with long course.it makes patients suffer great physical and psychotogical pain.At present, its difficult to heal the chronic skin ulcer,and the healing mechanism is not completely clear. This research aims to explore the mechanism of healing of chronic ulcer of skin from the level of molecular biology by laboratory and clinical research on the chronic skin ulcer.To further explore the working target of Chinese medicine treatm-ent, meanwhile,to confirm the effectiveness of cockroachextract liquid in treatment of chronic skin ulcer with objective data. The ultimate aim is to provide laboratory basis and data support for seeking the effective、convenient and inexpensive treatment of chronic skin ulcer.Methods:68sufferers who meet the inclusion criteria of chronic skin ulcer were randomly divided into experimental group and control group. the Infected patients should be given anti-infection treatment, the patients with diabetesmellit-us can also take hypoglycemic agents. clean the ulcer with physiological saline cotton, then wipe the ulcer with dry cotton, the experimental group sufferers were treated with cockroach extract liquid wet compress(Kangfuxin liquid),while spread the Shengjisan over the ulcer surface of control group sufferers, finally bandaged ulcer the with sterile gauze. The two groups were changed dressing everyday, for4weeks. To observe the healing course and cure rate. Before and after the treatment, took the skin lesions tissue samples of the two groups,the expression of Smad3gene、TGF-β1and VEGF was examined by immunohistochemistry method.Results:Before treatment, the skin lesion area、the score of Secretion、the score of skin lesions clour、the score of skin lesions odor、the score of soreness and asting plasma glucose level of both experimental group and control group were comparable,with no significant difference (P>0.05);After1,2,3,4weeks of treatment, the skin lesion area、the score of secretion、the score of skin lesions clour of both experimental group and control group were comparable,with no significant difference (P>0.05);After1,2weeks of treatment, the score of skin lesions clour of both experimental group and control group were comparable,with no significant difference(P>0.05), After3,4weeks of treatment, the score of skin lesions clour of experimental group were significantly lower than the control group date(P<0.05);t After1,2,3weeks of treatment, the score of soreness of both experimental group and control group were comparable,with no significant difference(P>0.05), After4weeks of treatment, the score of soreness of experimental group were obviously lower than the control group date (P<0.05);the cure rate. success rate、better rate and the rate of Inefficiency was8.82%、29.41%、47.06%and14.71%respectively；while the date for the control group was14.71%、26.47%、47.06%and11.76%respectively; for experimental group,the number of patients whose asting plasma glucose level below6.11umol/ml、between6.12and11.1umol/ml、 above11.2umol/ml was21、8and5,while the result of control group was23、6and5;for experimental group;the number of patients who had suffered bedridden or disabled in action、diabetes、varicose vein of lower limb、skin injure or radiation was3、13、3、7、21、2, while the number of control group patients was4、11、18、252; because of the cockroach extract liquid wet compress (Kangfuxin liquid),the patients who suffered pain or itching was1and2,because of theShengjisan,the patients who suffered pain or itching was2and2;for the patients of both experimental group and control group,about60%of them was between41～50years old and between51～60years old.Before treatment, for the experimental group,the percentage of Smad3gene、TGF-β1and VEGF was79.62±5.26%、29.74±3.12%、21.65±3.12%; for the control group, the the percentage of Smad3gene、TGF-β1and VEGF expressed positive cells was78.32±4.97%、29.13±3.98%、22.44±3.11%、 After4weeks of treatment, for the experimental group,the Smad3gene、TGF-β1and VEGF was18.85±1.88%、79.07±7.80%、59.24±3.74.%；for the control group, the date was20.03±2.42%,77.47±7.68%、61.09±4.10%. Before treatment,the expressed positive cells of Smad3gene、TGF-β1and VEGF in both experimental group and control group were comparable,with no significant difference (P>0.05);after the treatment for4weeks,the expressed positive cells of Smad3gene in experimental group is fewer than the control group obviously (P<0.05),while the TGF-β1and VEGF were more than control group obviously (P<0.05);when Completed the experiment,the expressed positive cells of Smad3gene reduce, and the expressed positive cells of TGF-β1and VEGF increased obviously (P<0.05).Conclusion:1. cockroach extract liquid can promote wound healing, clinical curative effect of cockroach extract liquid was similar to that of control group; after treatment, the skin lesion area、the score of Secretion、the score of skin lesions odor、success rate、better rate and the rate of Inefficiency of both experimental group and control group has no obvious difference; three indicators of clinical curative effect including the score of skin lesions soreness. the score of skin lesions clour and the cure rate of experimental group is better than the control group; the asting plasma glucose level and medical history analysis of the two groups has no obvious difference;3cases in experimental group and4cases in control group complainof pain or itching after treatment;In cases of the experimental group and control group, the cases who were41to50years old and up to51-60years old were accounted for about60%of the total. The treatment of cockroach extract liquid for chronic skin ulcer is effective, safe.2.cockroach extract liquid probably inhibit the expression of Smad3gene, meanwhile,promote the TGF-β1, VEGF generation and migration, promote newborn of ulcer granulation tissue and regeneration of capillary, thus speed up the chronic skin ulcer healing.更多还原