【摘要】：目的:BMOV作為一種具有潛力治療糖尿病的藥物,已經(jīng)顯示了良好的降糖活性,由于BMOV中含有金屬釩,其毒副作用尚未完全闡明,它對(duì)糖尿病大鼠降低血糖之外的作用有待深入研究。氧化應(yīng)激是糖尿病并發(fā)癥的重要危險(xiǎn)因素,目前關(guān)于BMOV與糖尿病大鼠機(jī)體氧化應(yīng)激作用方面的研究較少,而肝臟作為糖脂代謝和機(jī)體氧化應(yīng)激的主要器官,BMOV對(duì)于糖尿病所引起肝臟損傷的作用值得進(jìn)一步研究。本研究初步探討B(tài)MOV對(duì)于糖尿病大鼠肝臟及氧化應(yīng)激作用的影響,為BMOV的進(jìn)一步研究提供參考依據(jù)。方法:本實(shí)驗(yàn)采用60只健康雄性清潔級(jí)Wistar大鼠,體重200-220 g,隨機(jī)選取50只大鼠,用STZ誘導(dǎo)糖尿病模型,以隨機(jī)血糖≥16.7 mmol/L為判斷糖尿病大鼠造模成功的標(biāo)準(zhǔn)。將成模大鼠隨機(jī)分為5組分別為:0.25mg BMOV組(0.25mg/kg·d)、0.5 mg BMOV組(0.5mg/kg·d)、1 mg BMOV組(1mg/kg·d)、陽性對(duì)照組(1.5 mg/kg·d優(yōu)降糖)和糖尿病模型組(等劑量生理鹽水),剩余10只為正常對(duì)照組(等劑量生理鹽水),進(jìn)行連續(xù)3周灌胃。每周測量大鼠體重、血糖,實(shí)驗(yàn)結(jié)束采集大鼠血清及肝臟組織,檢測6組大鼠糖化血清蛋白、甘油三酯、膽固醇、低密度脂蛋白、高密度脂蛋白、超氧化物歧化酶、谷胱甘肽過氧化物酶、丙二醛、谷丙轉(zhuǎn)氨酶、谷草轉(zhuǎn)氨酶水平,體長、肝臟重量等指標(biāo),HE染色觀察大鼠肝臟組織形態(tài),免疫組織化學(xué)法染色檢測NF-κB和TNF-α的表達(dá)。結(jié)果:(1)BMOV 0.25mg組、0.5mg組、1mg組、陽性對(duì)照組和糖尿病模型組體重和體長低于正常對(duì)照組(P0.05);不同組間大鼠lee’s指數(shù)無統(tǒng)計(jì)學(xué)差異(P0.05)。(2)BMOV 0.25mg、0.5mg、1mg組和陽性對(duì)照組給藥后,血糖均呈現(xiàn)下降趨勢,而糖尿病模型組大鼠血糖未見明顯變化。BMOV 0.25mg、0.5mg、1mg組、陽性對(duì)照組和糖尿病模型組糖化血清蛋白高于正常對(duì)照組(P0.05)。(3)BMOV 0.25mg、0.5mg、1mg組、陽性對(duì)照組、糖尿病模型組及正常對(duì)照組大鼠血清甘油三酯、膽固醇、低密度脂蛋白、高密度脂蛋白水平均無統(tǒng)計(jì)學(xué)差異(P0.05)(4)6組大鼠血清超氧化物歧化酶(SOD)活力差異無統(tǒng)計(jì)學(xué)意義(P0.05);BMOV 0.25mg組、0.5mg組血清谷胱甘肽過氧化物酶(GSH-Px)活力高于糖尿病模型組(P0.05),與陽性對(duì)照組和正常對(duì)照組相比無統(tǒng)計(jì)學(xué)差異(P0.05),而BMOV1mg組血清GSH-Px活力低于陽性對(duì)照組和正常對(duì)照組(P0.05),與糖尿病模型組相比無統(tǒng)計(jì)學(xué)差異(P0.05);BMOV 0.25mg組大鼠血清丙二醛(MDA)水平低于糖尿病模型組(P0.05),BMOV0.5mg組、1mg組血清MDA水平高于正常對(duì)照組(P0.05)。(5)6組間大鼠血清谷丙轉(zhuǎn)氨酶(ALT)和谷草轉(zhuǎn)氨酶(AST)水平差異無統(tǒng)計(jì)學(xué)意義(P0.05)。與正常對(duì)照組大鼠肝臟組織相比,BMOV 0.25mg、0.5mg、1mg組、陽性對(duì)照組和糖尿病模型組大鼠肝臟有脂肪空泡和糖原空洞,BMOV 1mg組存在炎性細(xì)胞侵潤現(xiàn)象,BMOV 0.25mg、0.5mg、1mg組、陽性對(duì)照組和糖尿病模型組大鼠肝臟均有不同程度損傷。(6)免疫組化染色結(jié)果顯示:BMOV 0.25mg組、0.5mg組、1mg組、陽性對(duì)照組和糖尿病模型組大鼠肝臟NF-κB表達(dá)量均高于正常對(duì)照組。BMOV 0.25mg組、0.5mg組、1mg組、陽性對(duì)照組和糖尿病模型組TNF-α表達(dá)量均高于正常對(duì)照組,細(xì)胞質(zhì)中棕黃色顆粒增多,其中,BMOV 0.25mg組肝細(xì)胞中棕黃色顆粒少于糖尿病模型組。隨BMOV實(shí)驗(yàn)劑量增加,NF-κB和TNF-α表達(dá)量呈現(xiàn)增加趨勢。結(jié)論:1、在BMOV1.0mg/kg·d及以下尚不能有效的降低糖尿病大鼠血糖,但血糖已呈現(xiàn)降低趨勢。2、劑量為0.25mg/kg·d的BMOV,能夠提高糖尿病大鼠谷胱甘肽過氧化物酶活力,降低糖尿病大鼠機(jī)體丙二醛水平,改善糖尿病大鼠機(jī)體氧化應(yīng)激水平,提高抗氧化能力。3、劑量為1mg/kg·d的BMOV,導(dǎo)致糖尿病大鼠谷胱甘肽過氧化物酶活力水平降低,丙二醛水平升高,該劑量可能導(dǎo)致糖尿病大鼠機(jī)體氧化應(yīng)激作用增強(qiáng)。4、隨BMOV實(shí)驗(yàn)劑量的增大,對(duì)糖尿病大鼠肝臟損傷作用呈現(xiàn)增強(qiáng)趨勢。
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R965

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本文編號(hào)：2199068