摘要
目的观察清利活血汤配合三黄生肌纱条对糖尿病足大鼠溃疡肉芽组织基质金属蛋白酶9(MMP-9)、组织金属蛋白酶抑制剂-1(TIMP-1)、超氧化物歧化酶(SOD)及丙二醛(MDA)的干预作用,探讨其促进溃疡愈合的作用机制。方法将32只雄性Wistar大鼠随机分为模型对照组、正常对照组、清利活血汤治疗组及二甲双胍对照组4组,各8只。除正常对照组予正常饲料喂养外,其余各组均用高脂饲料喂养4周后,腹腔注射链脲佐菌素(STZ)30 mg/kg制作2型糖尿病模型,造模成功后4组动物以10%水合氯醛1mL/100 g体质量腹腔注射麻醉下大鼠背部脊柱左侧相同部位制作直径2 cm溃疡,分笼饲养。各组从术后第1 d开始灌胃给药及溃疡换药,清利活血汤治疗组予清利活血汤2 mL[14.5 g/(kg.d)],三黄生肌纱条换药,每日1次;二甲双胍对照组予盐酸二甲双胍片混悬液2 mL[72.4 mg/(kg.d)],凡士林纱条换药,每日1次;模型对照组和正常对照组予0.9%氯化钠注射液2 mL/(次.d),0.9%氯化钠注射液纱条换药,每日1次。用药15 d后处死大鼠,测定糖化血红蛋白(HbAlc)、MMP-9、TIMP-1、SOD及MDA含量。结果模型对照组HbAlc明显高于正常对照组(P<0.01);清利活血汤治疗组、二甲双胍对照组HbAlc低于模型对照组(P<0.01);清利活血汤治疗组HbAlc与二甲双胍对照组比较差异无统计学意义(P>0.05)。模型对照组大鼠创面肉芽组织MMP-9含量、MMP-9/TIMP-1均较正常对照组升高(P<0.01);清利活血汤治疗组、二甲双胍对照组大鼠创面肉芽组织MMP-9含量均较模型对照组降低(P<0.01),且清利活血汤治疗组降低明显(P<0.01)。与正常对照组比较,其余各组大鼠创面肉芽组织TIMP-1含量均升高,但比较差异无统计学意义(P>0.05)。与模型对照组比较,清利活血汤治疗组、二甲双胍对照组MMP-9/TIMP-1值均降低,但比较差异无统计学意义(P>0.05)。与正常对照组比较,模型对照组大鼠创面肉芽组织SOD含量明显降低(P<0.01),MDA含量明显升高(P<0.01);与模型对照组比较,清利活血汤治疗组、二甲双胍对照组大鼠创面肉芽组织SOD含量均明显升高(P<0.01),MDA含量均明显降低(P<0.01),且清利活血汤治疗组大鼠创面肉芽组织SOD、MDA含量改善明显(P<0.05)。结论清利活血汤配合三黄生肌纱条可降低糖尿病足大鼠溃疡肉芽组织MMP-9、MDA含量,提高SOD含量,从而加速溃疡愈合,其疗效优于二甲双胍+凡士林。
Objective To investigate the effect of Qinglihuoxue decoction combined with Sanhuangshengji gauze on MMP-9,TIMP-1,SOD and MDA in ulcers granulation tissue of rats with diabetic foot.Methods 32 male Wistar rats were randomly divided into model control group,normal control group,Qinglihuoxue decoction treatment group and metformin control group,8 rats in each group.In addition to the normal control group received the normal feeding and other groups were fed with high fat diet for 4 weeks then intraperitoneal injection of streptozotocin（STZ） 30 mg/kg produced type 2 diabetes model.After the modeling,under anesthesia of four groups of animals were injected intraperitoneally with 10% chloral hydrate 1 mL/100 g body quality the back spine of the left side the same parts in rats induced a ulcer of 2 cm diameter.From postoperative day 1,rats in four groups were administered orally and received ulcer medication.Qinglihuoxue decoction treatment group received Qinglihuoxue decoction 2 mL（14.5 g/kg·d） and Sanhuangshengji gauze dressing change and metformin control group received metformin suspension 2 mL（72.4 mg/kg·d） and Vaseline gauze dressing change.Model control group and normal control group received 2 mL（0.9% NaCl solution） and 0.9% NaCl solution gauze dressing change.The contents of glycosylated hemoglobin（HbAlc）,MMP-9,TIMP-1,SOD and MDA were determined rats were sacrificed after 15 days of medication.Results HbAlc in model control group was higher than that in normal control group（P0.01）.HbAlc in Qinglihuoxue decoction treatment group and metformin control group was higher than that in model control group（P0.01）.The contents of MMP-9 and MMP-9/TIMP-1 in granulation tissue in model control group were increased as compared with those in normal control group（P0.01）.The contents of MMP-9 and MMP-9/TIMP-1 in granulation tissue Qinglihuoxue decoction treatment group and metformin control group were decreased as compared with those in model control group（P0.01）.The decrease of Qinglihuoxue decoction treatment group was more obviously（P0.01）.The contents of TIMP-1 in granulation tissue in other groups were increased as compared with that in normal control group,but there was no significant difference（P0.05）.As compared with that in model control group,MMP-9/TIMP-1 ratio in Qinglihuoxue decoction treatment group and metformin control group was decreased,but there was no significant difference（P0.05）.As compared with that in normal control group,the content of SOD in granulation tissue in model control group was significantly decreased（P0.05）.As compared with that in model control group,the content of SOD in granulation tissue in Qinglihuoxue decoction treatment group and metformin control group was significantly increased（P0.01）.The content of MDA was obviously decreased（P0.01）.The improvement of the contents of SOD and MDA in rat granulation tissue in Qinglihuoxue decoction treatment group was obvious（P0.05）.Conclusion Qinglihuoxue decoction combined with Sanhuangshengji gauze can decrease the contents of MMP-9 and MDA in granulation tissue of rat with diabetic foot,increase SOD content and accelerate ulcer healing,its effect was superior to that in metformin combined with Vaseline.
出处
《河北中医》
2012年第2期274-277,299,共5页
Hebei Journal of Traditional Chinese Medicine
基金
河北省中医药管理局2010年度中医药类科研计划课题(编号:2010081)
关键词
溃疡
肉芽组织
基质金属蛋白酶9
超氧化物歧化酶
丙二醛
中药疗法
疾病模型
动物
糖尿病
Ulcer
Granulation tissue
Matrix Metalloproteinase 9
Superoxide dismutase
Malondialdehyde
Chinese Medicine Therapy
Disease model
Animal
Diabetes
