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小剂量联麦氧钒对糖尿病大鼠肝脏及机体氧化应激影响的研究

发布时间:2018-08-23 12:22
【摘要】:目的:BMOV作为一种具有潜力治疗糖尿病的药物,已经显示了良好的降糖活性,由于BMOV中含有金属钒,其毒副作用尚未完全阐明,它对糖尿病大鼠降低血糖之外的作用有待深入研究。氧化应激是糖尿病并发症的重要危险因素,目前关于BMOV与糖尿病大鼠机体氧化应激作用方面的研究较少,而肝脏作为糖脂代谢和机体氧化应激的主要器官,BMOV对于糖尿病所引起肝脏损伤的作用值得进一步研究。本研究初步探讨BMOV对于糖尿病大鼠肝脏及氧化应激作用的影响,为BMOV的进一步研究提供参考依据。方法:本实验采用60只健康雄性清洁级Wistar大鼠,体重200-220 g,随机选取50只大鼠,用STZ诱导糖尿病模型,以随机血糖≥16.7 mmol/L为判断糖尿病大鼠造模成功的标准。将成模大鼠随机分为5组分别为:0.25mg BMOV组(0.25mg/kg·d)、0.5 mg BMOV组(0.5mg/kg·d)、1 mg BMOV组(1mg/kg·d)、阳性对照组(1.5 mg/kg·d优降糖)和糖尿病模型组(等剂量生理盐水),剩余10只为正常对照组(等剂量生理盐水),进行连续3周灌胃。每周测量大鼠体重、血糖,实验结束采集大鼠血清及肝脏组织,检测6组大鼠糖化血清蛋白、甘油三酯、胆固醇、低密度脂蛋白、高密度脂蛋白、超氧化物歧化酶、谷胱甘肽过氧化物酶、丙二醛、谷丙转氨酶、谷草转氨酶水平,体长、肝脏重量等指标,HE染色观察大鼠肝脏组织形态,免疫组织化学法染色检测NF-κB和TNF-α的表达。结果:(1)BMOV 0.25mg组、0.5mg组、1mg组、阳性对照组和糖尿病模型组体重和体长低于正常对照组(P0.05);不同组间大鼠lee’s指数无统计学差异(P0.05)。(2)BMOV 0.25mg、0.5mg、1mg组和阳性对照组给药后,血糖均呈现下降趋势,而糖尿病模型组大鼠血糖未见明显变化。BMOV 0.25mg、0.5mg、1mg组、阳性对照组和糖尿病模型组糖化血清蛋白高于正常对照组(P0.05)。(3)BMOV 0.25mg、0.5mg、1mg组、阳性对照组、糖尿病模型组及正常对照组大鼠血清甘油三酯、胆固醇、低密度脂蛋白、高密度脂蛋白水平均无统计学差异(P0.05)(4)6组大鼠血清超氧化物歧化酶(SOD)活力差异无统计学意义(P0.05);BMOV 0.25mg组、0.5mg组血清谷胱甘肽过氧化物酶(GSH-Px)活力高于糖尿病模型组(P0.05),与阳性对照组和正常对照组相比无统计学差异(P0.05),而BMOV1mg组血清GSH-Px活力低于阳性对照组和正常对照组(P0.05),与糖尿病模型组相比无统计学差异(P0.05);BMOV 0.25mg组大鼠血清丙二醛(MDA)水平低于糖尿病模型组(P0.05),BMOV0.5mg组、1mg组血清MDA水平高于正常对照组(P0.05)。(5)6组间大鼠血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平差异无统计学意义(P0.05)。与正常对照组大鼠肝脏组织相比,BMOV 0.25mg、0.5mg、1mg组、阳性对照组和糖尿病模型组大鼠肝脏有脂肪空泡和糖原空洞,BMOV 1mg组存在炎性细胞侵润现象,BMOV 0.25mg、0.5mg、1mg组、阳性对照组和糖尿病模型组大鼠肝脏均有不同程度损伤。(6)免疫组化染色结果显示:BMOV 0.25mg组、0.5mg组、1mg组、阳性对照组和糖尿病模型组大鼠肝脏NF-κB表达量均高于正常对照组。BMOV 0.25mg组、0.5mg组、1mg组、阳性对照组和糖尿病模型组TNF-α表达量均高于正常对照组,细胞质中棕黄色颗粒增多,其中,BMOV 0.25mg组肝细胞中棕黄色颗粒少于糖尿病模型组。随BMOV实验剂量增加,NF-κB和TNF-α表达量呈现增加趋势。结论:1、在BMOV1.0mg/kg·d及以下尚不能有效的降低糖尿病大鼠血糖,但血糖已呈现降低趋势。2、剂量为0.25mg/kg·d的BMOV,能够提高糖尿病大鼠谷胱甘肽过氧化物酶活力,降低糖尿病大鼠机体丙二醛水平,改善糖尿病大鼠机体氧化应激水平,提高抗氧化能力。3、剂量为1mg/kg·d的BMOV,导致糖尿病大鼠谷胱甘肽过氧化物酶活力水平降低,丙二醛水平升高,该剂量可能导致糖尿病大鼠机体氧化应激作用增强。4、随BMOV实验剂量的增大,对糖尿病大鼠肝脏损伤作用呈现增强趋势。
[Abstract]:OBJECTIVE: As a potential drug for diabetes mellitus, BMOV has shown good hypoglycemic activity. The toxicity and side effects of BMOV have not been fully elucidated. The effect of BMOV on diabetic rats in addition to reducing blood sugar needs further study. Oxidative stress is an important risk factor for diabetic complications. The effect of BMOV on diabetic liver and oxidative stress in diabetic rats is worthy of further study. Methods: 60 healthy male Wistar rats weighing 200-220 g were randomly selected and 50 diabetic rats were induced by STZ. Random blood glucose (>16.7 mmol/L) was used as the criterion to judge the success of diabetic rats. D), 0.5 mg BMOV group (0.5 mg/kg.d), 1 mg BMOV group (1 mg/kg.d), positive control group (1.5 mg/kg.d euglycemic hypoglycemia) and diabetes mellitus model group (equal dose of normal saline), the remaining 10 normal control group (equal dose of normal saline) were given gastric perfusion for three weeks. Serum glycosylated protein, triglyceride, cholesterol, low density lipoprotein, high density lipoprotein, superoxide dismutase, glutathione peroxidase, malondialdehyde, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, body length, liver weight and other indicators were observed by HE staining, and NF-kappa B and TN were detected by immunohistochemical staining. Results: (1) BMOV 0.25 mg group, 0.5 mg group, 1 mg group, positive control group and diabetic model group had lower body weight and body length than normal control group (P BMOV 0.25 mg, 0.5 mg, 1 mg group, positive control group and diabetic model group were higher than normal control group (P 0.05). (3) BMOV 0.25 mg, 0.5 mg, 1 mg group, positive control group, diabetic model group and normal control group were higher in serum triglyceride, cholesterol, low density lipoprotein, high density lipoprotein levels. There was no significant difference in the activity of serum superoxide dismutase (SOD) among the 6 groups (P 0.05) (4); the activity of serum glutathione peroxidase (GSH-Px) in BMOV 0.25 mg group and 0.5 mg group was higher than that in diabetic model group (P 0.05), and there was no significant difference between positive control group and normal control group (P 0.05), but the activity of serum GS in BMOV 1 mg group was higher than that in diabetic model group (P 0.05). The level of serum malondialdehyde (MDA) in BMOV 0.25 mg group was lower than that in diabetic model group (P 0.05), BMOV 0.5 mg group, and 1 mg group was higher than that in normal control group (P 0.05). Compared with normal control group, BMOV 0.25 mg, 0.5 mg, 1 mg group, positive control group and diabetic model group had fat vacuoles and glycogen cavities in the liver, BMOV 1 mg group had inflammatory cell invasion, BMOV 0.25 mg, 0.5 mg, 1 mg group, positive control group and diabetic model group. The results of immunohistochemical staining showed that the expression of NF-kappa B in the liver of BMOV 0.25 mg group, 0.5 mg group, 1 mg group, positive control group and diabetic model group was higher than that of normal control group. The expression of TNF-a in BMOV 0.25 mg group, 0.5 mg group, 1 mg group, positive control group and diabetic model group was higher than that of normal control group. The expression of NF-kappa B and TNF-alpha increased with the increase of BMOV dosage. Conclusion: 1. BMOV 1.0 mg/kg/d and below can not effectively reduce blood glucose in diabetic rats, but blood glucose has shown a decreasing trend. BMOV with dosage of 0.25 mg/kg/d could increase the activity of glutathione peroxidase, decrease the level of malondialdehyde, improve the oxidative stress and antioxidant capacity of diabetic rats. BMOV with dosage of 1 mg/kg/d could decrease the activity of glutathione peroxidase and malondialdehyde in diabetic rats. The increase of aldehyde level may lead to the increase of oxidative stress in diabetic rats. 4. With the increase of BMOV dosage, the liver injury in diabetic rats tends to increase.
【学位授予单位】:吉林大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R965

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