银杏异双黄酮改善糖尿病大鼠足溃疡创面愈合的机制研究

Study on wound healing mechanism of the foot ulcer in diabetic rats by isoginkgetin

目的探讨银杏异双黄酮对糖尿病大鼠足溃疡创面愈合的影响,并分析其作用机制。方法雄性SD大鼠随机分为正常对照组、糖尿病模型组和银杏异双黄酮干预组,每组10只。链脲佐菌素(STZ)腹腔注射诱导大鼠糖尿病(正常对照组给予相同剂量腹腔注射0.1 M柠檬酸钠),诱导6周后,对各组大鼠背部切皮形成创面,并开放创面24 h。其后银杏异双黄酮干预组大鼠每天喷涂1 mM的银杏异双黄酮溶液0.1 mL,正常对照组及糖尿病模型组分别用0.1 mL生理盐水喷涂,连续14 d。分别于第7、14天测量血糖水平和体质量,同时评估创口面积,计算愈合率。干预后第14天,大鼠麻醉后安乐死,切取组织形成组织匀浆,ELISA检测组织中TGF-β1、VEGF、MMP-9及TIMP-1的含量。结果STZ造模后,大鼠血糖水平显著升高,银杏异双黄酮可有效降低血糖水平,提高体质量,且在第7、14天银杏异双黄酮干预组的创面愈合率高于糖尿病模型组(P<0.05),ELISA检测银杏异双黄酮干预组TGF-β1、VEGF含量均较糖尿病模型组高(P<0.05),MMP-9含量较糖尿病模型组低(P<0.05),而TIMP-1含量与糖尿病模型组比较差异无统计学意义(P>0.05)。结论银杏异双黄酮可通过提高局部生长因子TGF-β1和VEGF的表达水平,并降低MMP-9以及MMP-9/TIMP-1比值,以促进糖尿病足溃疡创面的愈合。

Objective Explore the effects of isoginkgetin on the healing of foot ulcer in diabetic rats and analyze the underlying mechanisms.Methods Male SD rats were randomly divided into normal control group,diabetes model group and isoginkgetin intervention group,with 10 rats in each group.Streptozotocin(STZ)was intraperitoneally injected to induce diabetes in rats(the normal control group was given the same dose of 0.1 m sodium citrate intraperitoneally).6 weeks later after induction,the back of rats in each group were cut to form wound surface which was opened for 24 h.Then the rats in the isoginkgetin intervention group were sprayed with 0.1 mL of 1 mm isoginkgetin solution every day,and the normal control group and the diabetes model group were sprayed with 0.1 mL of normal saline for 14 consecutive days.Blood glucose level and body mass were measured on the 7 th day and the 14 th day respectively,and wound area was evaluated to calculate the healing rate.On the 14 th day after the intervention,the rats were anesthetized and euthanized.Their tissues were cut to form tissue homogenate,in which the TGF-β1,VEGF,MMP-9 and TIMP-1 were detected by ELISA.Results The blood glucose level of diabetic rats was significantly increased after the STZ modeling.Isoginkgetin can effectively lower blood sugar levels and increase body weight.On the 7 th and 14 th day,the wound healing rate of isoginkgetin intervention group was higher than that of diabetes model group(P<0.05).The levels of TGF-β1 and VEGF in the isoginkgetin intervention group were higher than those in the diabetes model group(P<0.05),and the MMP-9 content was lower than that in the diabetes model group(P<0.05).There was no significant difference between the diabetes group and the isoginkgetin intervention group(P>0.05).Conclusion Isoginkgetin can promote the wound healing of diabetic foot ulcer by increasing the expression levels of local growth factors TGF-β1 and VEGF and decreasing the content of MMP-9.