本文選題：聚ADP核糖聚合酶 + 3-氨基苯甲酰胺�。� 參考：《瀘州醫(yī)學(xué)院》2012年碩士論文

【摘要】：目的： 本實(shí)驗(yàn)主要通過(guò)聚ADP核糖聚合酶(poly ADP-ribose polymerase,PARP)抑制劑3-氨基苯甲酰胺(3-aminobenzene,3-AB)對(duì)鏈脲佐菌素（streptozotocin，STZ）誘導(dǎo)的糖尿病大鼠進(jìn)行干預(yù)，，觀察其晶狀體混濁程度的進(jìn)展以及對(duì)相關(guān)指標(biāo)的檢測(cè)，探討PARP抑制劑對(duì)延緩糖尿病大鼠晶狀體混濁的機(jī)制。 方法： 1、體重200±20g雄性Wistar大鼠40只，進(jìn)行裂隙燈檢查排除晶狀體病變。適應(yīng)性喂養(yǎng)3d后自由飲水，禁食24h，隨機(jī)抽取9只作為正常對(duì)照組(A組)，腹腔注射0.1mol/L檸檬酸鹽緩沖液（50mg/kg，pH4.5）,其余大鼠則予以腹腔注射1%鏈脲佐菌素(Stretozocin, STZ)檸檬酸緩沖液（0.1mol/L檸檬酸鹽緩沖液臨時(shí)配制，pH4.5）。3d后尾靜脈取血，測(cè)得空腹血糖≥16.7mmol/L為糖尿病大鼠。 2、將糖尿病大鼠隨機(jī)分為糖尿病組（B組）和3-氨基苯甲酰胺干預(yù)組（C組）。自建立模型后第三天起，C組每日給予3-AB30mg/kg灌胃，A組和B組每天給予等體積0.9%N.S灌胃。實(shí)驗(yàn)中觀察記錄大鼠體重等一般情況，每周檢測(cè)一次空腹血糖。 3、1%復(fù)方托品酰胺眼液充分散瞳后在裂隙燈下觀察并記錄各組晶狀體混濁進(jìn)展情況，每周一次，記錄參照國(guó)外醫(yī)學(xué)眼科學(xué)分冊(cè)的晶狀體混濁分級(jí)方法。分別于給藥后2w、4w、8w分批處死各組大鼠。每組各取3只眼球固定包埋后，做石蠟切片用于免疫組化SP法檢測(cè)晶狀體上皮細(xì)胞中基質(zhì)金屬蛋白-2(matrix metalloproteinase-2,MMP-2)和堿性成纖維細(xì)胞生長(zhǎng)因子(basic fibroblast growth factor,bFGF)的表達(dá)情況；另外3只分離晶狀體后分別檢測(cè)谷胱甘肽過(guò)氧化物酶（glutathione peroxidase,GSH-PX）和超氧化物歧化酶（superoxide dismutase,SOD）的活性以及丙二醛（maleicdialdehyde,MDA）和糖基化終末產(chǎn)物（advanced glycation end products,AGE）的含量。 結(jié)果： 1、選取9只作為正常對(duì)照組(A組)大鼠的生長(zhǎng)狀況良好,采用STZ制作糖尿病大鼠模型,最終18只納入實(shí)驗(yàn),均出現(xiàn)三多一少的典型糖尿病表現(xiàn)。 2、在實(shí)驗(yàn)2、4、8周，B、C組血糖高于A組，差異具有統(tǒng)計(jì)學(xué)意義(P＜0.01)，但B組與C組相比，血糖無(wú)差異(P＞0.05)。 3、在整個(gè)實(shí)驗(yàn)過(guò)程中，A組始終保持晶狀體透明，而隨著實(shí)驗(yàn)的進(jìn)行，3周時(shí)B組、C組均開(kāi)始出現(xiàn)不同程度的晶狀體混濁。4周和8周時(shí)A、B、C三組間晶狀體混濁程度有明顯差異(P＜0.01)，且4周和8周時(shí)B組晶狀體混濁程度比A組重(P＜0.01)。 4、免疫組化結(jié)果：MMP-2在A組幾乎沒(méi)有表達(dá)，而隨著實(shí)驗(yàn)的進(jìn)行B、C組表達(dá)逐漸增強(qiáng)，且B組強(qiáng)于C組(P＜0.01)；bFGF在A、B、C組則均呈陽(yáng)性表達(dá)，A組與B、C組之間表達(dá)有明顯差異(P＜0.01)，且B、C組隨著實(shí)驗(yàn)的進(jìn)行而增強(qiáng)，但B、C組之間bFGF的表達(dá)無(wú)差異(P＞0.05)。 5、氧化指標(biāo)的檢測(cè)：A組GSH-px和SOD的活性均高于B、C兩組(P＜0.01)，但在各時(shí)間段B組均低于C組(P＜0.01, P＜0.05)；MDA的含量在B、C組增加，與A組比較(P＜0.01)，且B組高于C組(P＜0.05)。 6、B、C組在各時(shí)間段AGE的含量均高于A組；在2周、4周時(shí)B組高于C組(P＜0.05)，但在8周時(shí)無(wú)差異(P＞0.05)。 結(jié)論： 1、PARP抑制劑3-AB對(duì)糖尿病大鼠晶狀體具有一定保護(hù)作用，可以延緩糖尿病性白內(nèi)障的發(fā)生發(fā)展。 2、PARP抑制劑3-AB通過(guò)減輕高糖所致的晶狀體上皮細(xì)胞氧化損傷和非酶糖基化水平而抑制晶狀體的混濁。 3、PARP抑制劑3-AB抑制MMP-2的表達(dá)減輕晶狀體上皮細(xì)胞外基質(zhì)降解，從而達(dá)到延緩糖尿病性白內(nèi)障的作用。 4、bFGF參與了糖尿病性白內(nèi)障的發(fā)生發(fā)展。
[Abstract]:Objective:
In this experiment, ADP ribose polymerase (poly ADP-ribose polymerase, PARP) inhibitor, 3- amino benzoformamide (3-aminobenzene, 3-AB), was used to interfere with streptozotocin (streptozotocin, STZ) induced diabetic rats. The progress of the degree of lens opacification and the detection of the related indexes were observed. The delay of the inhibitor was discussed. The mechanism of lens opacification in diabetic rats.
Method:
1, 40 male Wistar rats with weight of 200 20g were checked out of lens lesions by slit lamp examination. After feeding 3D free drinking water and fasting 24h, 9 rats were randomly selected as normal control group (A group) with 0.1mol/L citrate buffer (50mg/kg, pH4.5) intraperitoneally, and the rest rats were intraperitoneally injected with 1% streptozotocin (Stretozocin, STZ) lime (Stretozocin, STZ). Blood glucose was obtained from tail vein after citric acid buffer solution (0.1mol/L citrate buffer was temporarily formulated, pH4.5).3d, and fasting blood glucose (16.7mmol/L) was measured in diabetic rats.
2, diabetic rats were randomly divided into diabetes group (group B) and 3- amino benzamide intervention group (group C). From the third day after the establishment of the model, group C was given 3-AB30mg/kg gavage every day, and group A and B group were given equal volume of 0.9%N.S every day. The experiment observed the body weight of rats and other cases, and tested the fasting blood glucose once a week.
3,1% compound entrapment amide eye solution was fully scattered under the slit lamp, observed and recorded the progress of lens opacities in each group. Once a week, the lens turbidity classification method was recorded with reference to foreign medical ophthalmology division. The rats were killed in groups of 2W, 4W, and 8W after administration. Each group took 3 eyeballs and embedded to make paraffin slices. The expression of matrix metalloprotein -2 (matrix metalloproteinase-2, MMP-2) and basic fibroblast growth factor (basic fibroblast growth factor, bFGF) in lens epithelial cells was detected by immuno histochemical SP, and the other 3 separate lenses were used to detect the cereal caspase peroxidase (glutathione peroxidase,) and ultra The activity of oxide dismutase (superoxide dismutase, SOD) and the content of malondialdehyde (maleicdialdehyde, MDA) and the end products of glycosylation (advanced glycation end products, AGE).
Result:
1, the growth status of 9 rats in the normal control group (group A) was good, and the diabetic rat model was made with STZ, and the final 18 were included in the experiment.
2, at the experimental 2,4,8 weeks, the blood glucose in group B and C was higher than that in group A, the difference was statistically significant (P < 0.01), but there was no difference in blood glucose between B group and C group (P > 0.05).
3, during the whole experiment, the A group always kept the lens transparent, and with the experiment, the B group in the group of B and the group C began to appear different degree of lens opacities at the time of 3 weeks and the 8 weeks of A, B, and C three were significantly different (P < 0.01), and the degree of turbidity in the B group was heavier than the A group (P < 0.01) at the 4 and 8 weeks.
4, the results of immunohistochemistry: MMP-2 was almost not expressed in group A, but with the experiment of B, the expression of C group was increased gradually, and B group was stronger than group C (P < 0.01); bFGF in A, B, C group was positive, and there was a significant difference between A group and C group (0.01). P > 0.05).
5, the detection of oxidation index: the activity of GSH-px and SOD in group A was higher than that of B, C two (P < 0.01), but in each time period B group was lower than that of C group (P < 0.01, P < 0.05), MDA content was increased in B, and compared with that of the group (0.01), and the group was higher than that of the group (0.05).
6, the content of AGE in B and C groups was higher than that in group A at each time interval. At 2 weeks and 4 weeks, the B group was higher than that of C group (P < 0.05), but there was no difference at 8 weeks (P > 0.05).
Conclusion:
1, PARP inhibitor 3-AB has a certain protective effect on the lens of diabetic rats, and it can delay the occurrence and development of diabetic cataract.
2, PARP inhibitor 3-AB inhibits lens opacity by reducing the oxidative damage and non enzymatic glycosylation level of lens epithelial cells induced by high glucose.
3, PARP inhibitor 3-AB inhibits the expression of MMP-2 and alleviates the degradation of extracellular matrix in lens epithelial cells, thereby slowing the progression of diabetic cataract.
4, bFGF is involved in the occurrence and development of diabetic cataract.
【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R776.1

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