本文選題：左卡尼汀 + 糖尿病腎病��； 參考：《延邊大學(xué)》2017年碩士論文

【摘要】：目的:進(jìn)一步探討左卡尼汀對(duì)鏈脲霉素誘導(dǎo)的大鼠糖尿病腎病的保護(hù)作用及其機(jī)制。方法:實(shí)驗(yàn)SD大鼠隨機(jī)分為6組:正常對(duì)照組、左卡尼汀50mg/kg組(Con+L50)和左卡尼汀200mg/kg組(Con+L200),3組均腹腔內(nèi)注射生理鹽水(0.9%NS 1OmL/kg),靜脈注射兩種劑量的左卡尼汀12周;另分為DN模型組、DN+L50組和DN+L200組,均腹腔注射鏈脲霉素65mg/Kg誘導(dǎo)糖尿病腎病模型,靜脈注射兩種不同劑量左卡尼汀1次/day,共12周。實(shí)驗(yàn)開(kāi)始、每四周和實(shí)驗(yàn)結(jié)束時(shí)檢測(cè)全部的大鼠體重,尾靜脈采血和收集尿樣本,采用全自動(dòng)生化分析儀檢測(cè)各組大鼠空腹血糖(FBG)、血肌酐(Scr)及尿蛋白排泄量(UPE);酶聯(lián)免疫法測(cè)定尿8-羥基脫氧鳥(niǎo)苷(8-OHdG)排泄量。第12周末氯胺酮麻醉處死大鼠后取出腎臟,采用PAS染色方法觀察腎臟病理和檢測(cè)腎小球硬化指數(shù)(GSI),免疫組化觀察腎組織中ED-1陽(yáng)性細(xì)胞數(shù)和WT-1;電鏡觀察腎小球基底膜及足細(xì)胞形態(tài)及數(shù)量;測(cè)定腎組織中 MCP-1、TLR-2、TGF-β1、βig-h3、Bcl-2、Caspase-3、NF-κB、I-κB 和 MnSOD。結(jié)果:與正常組相比,DN模型大鼠體重明顯減輕(P0.05),而兩組不同劑量左卡尼汀治療后大鼠體重較DN模型組增加(均P0.05)與DN模型組比較,兩組左卡尼汀組大鼠Scr明顯降低及UPE減少(均P0.05);DN模型組大鼠空腹血糖與左卡尼汀兩組間比較均無(wú)統(tǒng)計(jì)學(xué)差異。與正常組相比 DN 組 MCP-1(100.6±2.4%vs 221.4±32.7%)、TLR-2(100.3±2.1%vs 168.4±29.3%)、TGF-β1(100.4 ±5.3%vs 279.2 ± 16.8%)、βig-h3(101.8 ±3.2%vs 230.2 ± 21.5%)、NF-κB(100.0 ± 3.7%vs 247.6 ± 23.3%)及Caspase-3(100.0 ±4.1%vs 169.8 ± 13.3%)表達(dá)增多(均p0.05,p0.01),而I-κB(100.0 ± 2.8%vs 49.8± 11.0%)和Bcl-2(100.0 ± 2.8%vs 43.6 ± 10.2%,P0.05)及MnSOD(100.5±2.7%vs 56.4±4.5%)表達(dá)降低(均p0.05orp0.01)。與正常組相比,DN組尿中8-OHdG排泄量增多(83.8±9.3ng/dayvs165.2±37.2ng/day,P0.05)。與DN模型組比較,左卡尼汀低劑量組MCP-1(DNvs183.2±17.9%)、TLR-2(DN vs 145.6±13.7%)和TGF-β1(DN vs 225.5 ± 2.6%)、βig-h3(DN vs 201.3 ±6.5%)、NF-κB(DNvs225.1±21.7%)和Caspase-3(DNvs143.7±6.7%)的表達(dá)下降,I-κB(DN vs 60.2± 5.9%)、Bcl-2(DN vs 143.7±6.7%)和 MnSOD(DN vs64.7±3.8%)表達(dá)增高(均p0.05),尿8-OHdG排泄量(DNvs228.3±12.9ng/day,P0.05)減少。而與左卡尼汀低劑量組比較,高劑量組上述指標(biāo)的改變更明顯。與正常對(duì)照組相比DN組腎臟病理表現(xiàn)為腎小球硬化,足細(xì)胞數(shù)量減少及足突融合、基底膜增厚,ED-1陽(yáng)性細(xì)胞數(shù)量增多,WT-1表達(dá)減少,與DN組比較左卡尼汀兩組腎小球硬化程度減輕,足細(xì)胞數(shù)量增多,足突結(jié)構(gòu)清楚,基底膜變薄,ED-1陽(yáng)性細(xì)胞數(shù)減少,WT-1表達(dá)增多。結(jié)論:左卡尼汀對(duì)鏈脲霉素誘導(dǎo)的大鼠糖尿病腎病具有良好的保護(hù)作用,其機(jī)制可能與左卡尼汀抑制炎癥,抗氧化及抑制凋亡相關(guān)。
[Abstract]:Objective: to further investigate the protective effect and mechanism of levocarnitine on streptozotamicin induced diabetic nephropathy in rats. Methods: the experimental SD rats were randomly divided into 6 groups: normal control group, levocarnitine 50mg/kg group (Con+L50) and L-carnitine 200mg/kg group (Con+L200). The 3 groups were intraperitoneally injected with saline (0.9%NS 1OmL/kg), and two kinds of intravenous injections were injected. The dose of levocarnitine for 12 weeks was divided into DN model group, DN+L50 group and DN+L200 group. The diabetic nephropathy model was induced by intraperitoneal injection of streptozotocin 65mg/Kg. Two different doses of levocarnitine were injected for 1 /day, for a total of 12 weeks. The experiment began to test the body weight of the whole rat, the tail vein blood collection and urine samples collected at the end of every four weeks and the end of the experiment. The fasting blood glucose (FBG), serum creatinine (Scr) and urinary protein excretion (UPE) were detected by an automatic biochemical analyzer. The excretion of 8- hydroxy deoxy guanosine (8-OHdG) was measured by ELISA. After twelfth weekend ketamine anesthesia was executed to remove the kidneys, the renal pathology and the glomerulosclerosis index (GSI) were detected by PAS staining method. The number of ED-1 positive cells and WT-1 in the renal tissue were observed by the Phytophthora, and the morphology and quantity of the glomerular basement membrane and podocyte were observed by electron microscopy, and MCP-1, TLR-2, TGF- beta 1, beta ig-h3, Bcl-2, Caspase-3, NF- kappa B, I- kappa B and the results were measured in the renal tissue. After treatment, the weight of rats was higher than that of the DN model group (P0.05). Compared with the DN model group, the Scr of the two groups was significantly reduced and UPE decreased (P0.05). There was no statistical difference between the rats in the DN model group and the two groups of levocarnitine. Compared with the normal group, the MCP-1 (100.6 + 2.4%vs 221.4 + 32.7%) and TLR-2 (100.3 + 1) were compared with that of the normal group. 68.4 + 29.3%), TGF- beta 1 (100.4 + 5.3%vs 279.2 + 16.8%), beta ig-h3 (101.8 + 3.2%vs 230.2 + 21.5%), NF- kappa B (100 + 3.7%vs 247.6 + 23.3%) and Caspase-3 (100 + 4.1%vs P0.05, P0.01), and I- kappa The expression of 2.7%vs 56.4 + 4.5%) decreased (p0.05orp0.01). Compared with the normal group, the urine 8-OHdG excretion in DN group increased (83.8 + 9.3ng/dayvs165.2 + 37.2ng/day, P0.05). Compared with the DN model group, the low dose group of levocarnitine was MCP-1 (DNvs183.2 + 17.9%), TLR-2 (DN 145.6 + 13.7%) and 1 (201.3 + 2.6%), and beta 1 (201.3 + 6.5%), The expression of F- kappa B (DNvs225.1 + 21.7%) and Caspase-3 (DNvs143.7 + 6.7%) decreased, I- kappa B (DN vs 60.2 + 5.9%), Bcl-2 (DN vs 143.7 + 6.7%) and Caspase-3 + 3.8% decreased, but compared with Levocarnitine low dose group, the changes of the above indexes in high dose group were more obvious. Compared with the normal control group, the renal pathological manifestations of the DN group were glomerulosclerosis, the number of podocytes and poddine fusion, the thickening of the basement membrane, the increase of the number of ED-1 positive cells, and the decrease of WT-1 expression. Compared with the group DN, the degree of glomerulosclerosis in the two groups of levocarnitine was reduced, the number of podocytes increased, the structure of the poddate was clear, the basement membrane thinned, and the ED-1 positive cells were changed. Conclusion: levocarnitine has a good protective effect on streptozotamicin induced diabetic nephropathy in rats. The mechanism may be related to the inhibition of inflammation, antioxidation and inhibition of apoptosis in levocarnitine.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R587.2;R692.9

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 Hiromichi Suzuki;Tomohiro Kikuta;Tsutomu Inoue;Ukihiro Hamada;;Time to re-evaluate effects of renin-angiotensin system inhibitors on renal and cardiovascular outcomes in diabetic nephropathy[J];World Journal of Nephrology;2015年01期

2 Samy L Habib;;Diabetes and renal tubular cell apoptosis[J];World Journal of Diabetes;2013年02期

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本文編號(hào)：2049036