芦荟凝胶治疗巴马小型猪糖尿病慢性皮肤溃疡的实验研究  

Experimental Study of Using Aloe Vera Gel to Treat Diabetic Chronic Cutaneous Ulcers in Bama Miniature Pigs

作　　者：梁渝捷 李艳[1] 高芸艺 王莉 冉兴无[1] LIANG Yu-jie;LI Yan;GAO Yun-yi;WANG Li;RAN Xing-wu(Innovation Center for Wound Repair,Diabetic Foot Care Center,Department of Endocrinology and Metabolism,West China Hospital,Sichuan University,Chengdu 610041,China;West China-Frontier PharmaTech Co.Ltd.(National Chengdu Center for Safety Evaluation of New Drugs),Chengdu 610041,China)

机构地区：[1]四川大学华西医院内分泌代谢科糖尿病足诊治中心创面修复创新中心,成都610041 [2]成都华西海圻医药科技有限公司(国家成都新药安全性评价中心),成都610041

出　　处：《四川大学学报（医学版）》2022年第6期953-960,共8页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金面上项目(No.81471043);四川大学华西医院1.3.5工程项目(No.ZYGD18025)资助。

摘　　要：目的研究局部应用芦荟凝胶(AVG)治疗巴马小型猪糖尿病慢性皮肤溃疡的有效性、安全性及其作用机制。方法将糖尿病慢性皮肤溃疡模型猪随机分为芦荟凝胶每日给药(AVG QD)组、芦荟凝胶隔日给药(AVG QOD)组及糖尿病对照(DC)组;非糖尿病慢性皮肤溃疡模型猪设为非糖尿病对照(NDC)组。疗效评价指标包括创面完全愈合时间、肉芽生长率、愈合率以及皮肤病理组织学观察;以是否观察到不良反应评价安全性;同时检测创面肉芽组织miR21、miR29a、miR126、miR146a、miR155和miR210相对表达量的动态变化。结果①疗效评估:NDC组完全愈合时间比DC组、AVG QD组及AVG QOD组短(P均<0.05),AVG QD组和AVG QOD组完全愈合时间较DC组短(P均<0.05),AVG QOD组完全愈合时间较AVG QD组短(P<0.05),芦荟凝胶治疗全过程未监测到不良反应发生。NDC组肉芽生长率高于DC组、AVG QD组及AVG QOD组(P均<0.05)。NDC组创面愈合率高于DC组、AVG QD组及AVG QOD组(P均<0.05);AVG QOD组创面愈合率高于DC组与AVG QD组(P均<0.05)。②组织病理学:HE染色光镜结果示AVG治疗后,创面愈合初期胶原纤维生成增多,真皮间质见微血管形成伴少许炎细胞浸润;完全愈合至一年后,表皮角化完全,胶原排列整齐有序,间质内见较多微血管分布。苦味酸天狼猩红特染结果示创面愈合初期以Ⅰ型胶原增多为主,至创面完全愈合时Ⅲ型胶原逐渐增多,整个过程胶原排列整齐有序。③microRNAs相对表达量:NDC组、AVG QD组及AVG QOD组miR21、miR126及miR210相对表达量均高于DC组(P均<0.05),miR29a、miR155相对表达量低于DC组(P均<0.05);NDC组miR146a相对表达量高于DC组(P<0.05)。结论芦荟凝胶局部治疗可以缩短巴马小型猪糖尿病慢性创面完全愈合时间,且隔日治疗组完全愈合时间快于每日治疗组,治疗过程中未发现不良反应发生,机制可能与其上调创面肉芽组织miR21、miR126及miR210表达,降低miR29a和mObjective To investigate the efficacy,safety,and mechanism of topical application of aloe vera gel(AVG)to treat diabetic chronic cutaneous ulcers in Bama miniature pigs.Methods The Bama miniature pig model of diabetic chronic skin wounds was constructed and the model pigs were randomly assigned to AVG daily administration group(AVG QD),aloe vera gel every-other-day administration group(AVG QOD),and diabetic control group(DC).A non-diabetic chronic skin wounds model pig was set as the non-diabetic control group(NDC).Treatment efficacy was evaluated based on the amount of time needed for complete healing of the wounds,healing rates,granulation growth rates,and skin histopathological changes.Safety was evaluated according to whether adverse reactions were observed.In addition,the dynamic changes of the relative expression levels of miR21,miR29a,miR126,miR146a,miR155,and miR210 in wound granulation tissues were examined.Results (1)Efficacy and safety:The amount of time needed for complete healing of the wounds was shorter in the NDC group than those of the three other groups,DC group,AVG QD group,and AVG QOD group(all P<0.05).The amount of time needed for complete healing of the wounds was shorter in the AVG QD group and AVG QOD group than that of DC group(all P<0.05).The amount of time needed for complete healing of the wounds was shorter in the AVG QOD group than that of AVG QD group(all P<0.05).No adverse reactions were detected in the whole process of AVG topical treatment.The granulation growth rate of NDC group was higher than those of DC group,AVG QD group,and AVG QOD group(all P<0.05).The wound healing rate of NDC group was higher than those of DC group,AVG QD group,and AVG QOD group(all P<0.05);the wound healing rate of AVG QOD group was higher than those of DC group and AVG QD group(all P<0.05).(2)Histopathology:The results of HE staining light microscopy showed that collagen fiber production increased,and that microvascular formation with slight inflammatory cell infiltration was observed in the dermal int

关 键 词：芦荟凝胶 巴马小型猪 糖尿病 慢性皮肤溃疡 MICRORNAS 创面愈合 

分 类 号：R587.2[医药卫生—内分泌]