积雪草总苷对糖尿病皮肤溃疡大鼠的促愈合作用研究
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摘要
目的本实验探讨积雪草总苷对大鼠糖尿病皮肤溃疡创面修复的影响。方法 38只雄性清洁级SD大鼠,随机分为正常组和模型组,代谢笼单笼饲养;模型组采用腹腔注射链脲佐菌素——全程皮肤缺损方法建立糖尿病皮肤溃疡(DCU)模型;模型建立后分别用低(22.29 mg·cm~(-2))、中(111.45 mg·cm~(-2))、高(222.93 mg·cm~(-2))剂量积雪苷霜软膏对DCU大鼠进行药物干预。治疗后3、7、10、14 d监测大鼠体重、血糖、饮水量及尿量;采用Adobe Photoshop CS5图像处理软件评价创面愈合率;利用HE染色观察DCU大鼠创面肉芽组织形态变化、上皮化、成纤维细胞增殖和血管新生。结果模型组大鼠体重、血糖与正常组比较有统计学差异(P<0.05);模型组大鼠尿量和饮水量均显著高于正常组;给药组创面愈合率高于模型对照组(P<0.01),以中剂量积雪苷霜软膏愈合效果最好(P<0.01);给药后创面肉芽组织生成增多,中剂量组上皮化较早及较高的成纤维细胞增殖,14 d表皮结构趋于完整。结论初步判断积雪草总苷对糖尿病皮肤溃疡大鼠创面具有促愈合作用。
OBJECTIVE To investigate the treatment effects of chronic ulcer in diabetic rats with asiaticosides. METHODS Totally 38 male CL grade SD rats were randomly divided into normal group and model group,and were feed in metabolic cage separately.The low( 22. 29 mg·cm~(-2)),medium( 111. 45 mg·cm~(-2)) and high( 222. 93 mg·cm~(-2)) dose of centella triterpenes cream were characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. After treatment,the weight,blood glucose,water intake and total urine output were measured in 3,7,10 and 14 d respectively. The wound healing rate was evaluated by image processing software of Adobe Photoshop CS5. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation,fibroblast proliferation and angiogenesis. RESULTS It was found that at all time points the areas of wounds treated with asiaticosides were smaller compared with the controls. The expression of weight,water intake,total urine output and blood glucose increased statistically in the model group( P < 0. 05). Pathological results showed much better healing efficacy for the test samples compared with the control ones( P < 0. 05). The middle dose of centella triterpenes cream was the best( P < 0. 01). Histopathological studies had also shown that centella triterpenes cream treated wounds exhibited re-epithelisation,higher fibroblast proliferation,collagen synthesis,and angiogenesis. At 14 days post excision,the medium centella triterpenes cream treated group achieved complete repair. CONCLUSION These findings suggest that asiaticosides may have a potential application in the treatment of diabetic ulcers and chronic wound healing.
OBJECTIVE To investigate the treatment effects of chronic ulcer in diabetic rats with asiaticosides. METHODS Totally 38 male CL grade SD rats were randomly divided into normal group and model group,and were feed in metabolic cage separately.The low( 22. 29 mg·cm~(-2)),medium( 111. 45 mg·cm~(-2)) and high( 222. 93 mg·cm~(-2)) dose of centella triterpenes cream were characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. After treatment,the weight,blood glucose,water intake and total urine output were measured in 3,7,10 and 14 d respectively. The wound healing rate was evaluated by image processing software of Adobe Photoshop CS5. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation,fibroblast proliferation and angiogenesis. RESULTS It was found that at all time points the areas of wounds treated with asiaticosides were smaller compared with the controls. The expression of weight,water intake,total urine output and blood glucose increased statistically in the model group( P < 0. 05). Pathological results showed much better healing efficacy for the test samples compared with the control ones( P < 0. 05). The middle dose of centella triterpenes cream was the best( P < 0. 01). Histopathological studies had also shown that centella triterpenes cream treated wounds exhibited re-epithelisation,higher fibroblast proliferation,collagen synthesis,and angiogenesis. At 14 days post excision,the medium centella triterpenes cream treated group achieved complete repair. CONCLUSION These findings suggest that asiaticosides may have a potential application in the treatment of diabetic ulcers and chronic wound healing.
引文
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[12]ZHAO G M,DONG J X,LI Y.Influence of Huiyang Shengji Formula on wound healing in rats with diabetic skin ulcer[J].J Beijing Univ Tradit Chin Med(北京中医药大学学报),2014,37(7):495-499.
[13]JHAMB S,VANGAVETI V N,MALABU U H.Genetic and molecular basis of diabetic foot ulcers:clinical review[J].J Tissue Viability,2016,pii:S0965-206X(16)30041-30049.
[14]LI B,LI F L,ZHAN K Q.Investgation of connective mathematics model on chronic cutaneous ulcer in traditional Chinese medicine syndrome differentiation[J].Chin J Dermatovenereol Integr Tradit West Med(中国中西医结合皮肤性病学杂志),2010,9(1):4-7.
[15]LI Y S,YANG B H.Effects of compound fluid of Cortex Phellodendri on inflammatory cytokines and growth factors in external treatment of diabetic foot ulcer[J].Chin J New Drugs(中国新药杂志),2014,23(10):1163-1166.
[16]CHEN W,YU K,WANG Y,et al.Pharmacological investigation of natural plant anti-microbial solution in treatment of mice with diabetic foot ulcers[J].J Chengdu Univ(成都中医药大学学报),2016,39(2):27-29.
[17]CAI Q X,WANG L,ZHANG Y,et al.Progress in the treatment of diabetic wound healing viastem cells transplant[J].Acta Pharm Sin(药学学报),2015,50(1):1-6.
[2]RICCO J B,THANH P L,SCHNEIDER F,et al.The diabetic foot:a review[J].J Cardiovasc Surg(Torino),2013,54(4):755-762.
[3]MARGOLIS D J,JEFFCOATE W.Epidemiology of foot ulceration and amputation:can global variation be explained[J].Med Clin North Am,2013,97(5):791-805.
[4]SNYRER R J,KIRSNER R S,WARRINER R A,et al.Consensus recommendations on advancing the standard of care for treating diabetic neuropathic foot ulcers in patients with diabetes[J].Ostomy Wound Manage,2010,56(4 suppl):1-24.
[5]HUANG Y H.Clinical research on treatment of chronic skin ulcer by chitosan multiple membrane[D].Harbin:Heilongjiang University of Chinese Medicine,2009.
[6]Ch.P(2015)VolⅠ(中国药典2015年版.一部)[S].2015:283-284.
[7]SAWATDEE S,CHOOCHUAY K,CHANTHORM W,et al.Evaluation of the topical spray containing Centella asiatica extract and its efficacy on excision wounds in rats[J].Acta Pharm,2016,66(2):233-244.
[8]SONG J,DAI Y,BIAN D,et al.Madecassoside induces apoptosis of keloid fi-broblasts via a mitochondrial-dependent pathway[J].Drug Develop Res,2011,72(4):315-322.
[9]DAI L B,PAN S,SHEN Y,et al.Effects of asiaticoside on dermal fibrous lasts in hypertrophic scar[J].Chin Pharm J(中国药学杂志),2010,45(14):1067-1772.
[10]PENG D M,LU R J,ZHAO S Y,et al.Study on reproducible rat model of ischemic diabetic ulcers[J].Pract Clin J Integr Tradit Chin West Med(实用中西医结合临床),2014,14(11):1-3.
[11]LI J H,WANG L,XI L H,et al.Effect of moxibustion on wound healing in rats with diabetic skin ulcer and its mechanism effect of moxibustion on wound healing in rats with diabetic skin ulcer and its mechanism[J].Guangxi Med J(广西医学),2015,37(12):1700-1704.
[12]ZHAO G M,DONG J X,LI Y.Influence of Huiyang Shengji Formula on wound healing in rats with diabetic skin ulcer[J].J Beijing Univ Tradit Chin Med(北京中医药大学学报),2014,37(7):495-499.
[13]JHAMB S,VANGAVETI V N,MALABU U H.Genetic and molecular basis of diabetic foot ulcers:clinical review[J].J Tissue Viability,2016,pii:S0965-206X(16)30041-30049.
[14]LI B,LI F L,ZHAN K Q.Investgation of connective mathematics model on chronic cutaneous ulcer in traditional Chinese medicine syndrome differentiation[J].Chin J Dermatovenereol Integr Tradit West Med(中国中西医结合皮肤性病学杂志),2010,9(1):4-7.
[15]LI Y S,YANG B H.Effects of compound fluid of Cortex Phellodendri on inflammatory cytokines and growth factors in external treatment of diabetic foot ulcer[J].Chin J New Drugs(中国新药杂志),2014,23(10):1163-1166.
[16]CHEN W,YU K,WANG Y,et al.Pharmacological investigation of natural plant anti-microbial solution in treatment of mice with diabetic foot ulcers[J].J Chengdu Univ(成都中医药大学学报),2016,39(2):27-29.
[17]CAI Q X,WANG L,ZHANG Y,et al.Progress in the treatment of diabetic wound healing viastem cells transplant[J].Acta Pharm Sin(药学学报),2015,50(1):1-6.