左卡尼汀对链脲霉素诱导的大鼠糖尿病肾病的保护作用

发布时间：2018-06-21 14:28

本文选题：左卡尼汀 + 糖尿病肾病　；参考：《延边大学》2017年硕士论文

【摘要】：目的:进一步探讨左卡尼汀对链脲霉素诱导的大鼠糖尿病肾病的保护作用及其机制。方法:实验SD大鼠随机分为6组:正常对照组、左卡尼汀50mg/kg组(Con+L50)和左卡尼汀200mg/kg组(Con+L200),3组均腹腔内注射生理盐水(0.9%NS 1OmL/kg),静脉注射两种剂量的左卡尼汀12周;另分为DN模型组、DN+L50组和DN+L200组,均腹腔注射链脲霉素65mg/Kg诱导糖尿病肾病模型,静脉注射两种不同剂量左卡尼汀1次/day,共12周。实验开始、每四周和实验结束时检测全部的大鼠体重,尾静脉采血和收集尿样本,采用全自动生化分析仪检测各组大鼠空腹血糖(FBG)、血肌酐(Scr)及尿蛋白排泄量(UPE);酶联免疫法测定尿8-羟基脱氧鸟苷(8-OHdG)排泄量。第12周末氯胺酮麻醉处死大鼠后取出肾脏,采用PAS染色方法观察肾脏病理和检测肾小球硬化指数(GSI),免疫组化观察肾组织中ED-1阳性细胞数和WT-1;电镜观察肾小球基底膜及足细胞形态及数量;测定肾组织中 MCP-1、TLR-2、TGF-β1、βig-h3、Bcl-2、Caspase-3、NF-κB、I-κB 和 MnSOD。结果:与正常组相比,DN模型大鼠体重明显减轻(P0.05),而两组不同剂量左卡尼汀治疗后大鼠体重较DN模型组增加(均P0.05)与DN模型组比较,两组左卡尼汀组大鼠Scr明显降低及UPE减少(均P0.05);DN模型组大鼠空腹血糖与左卡尼汀两组间比较均无统计学差异。与正常组相比 DN 组 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%)表达增多(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%)表达降低(均p0.05orp0.01)。与正常组相比,DN组尿中8-OHdG排泄量增多(83.8±9.3ng/dayvs165.2±37.2ng/day,P0.05)。与DN模型组比较,左卡尼汀低剂量组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%)的表达下降,I-κB(DN vs 60.2± 5.9%)、Bcl-2(DN vs 143.7±6.7%)和 MnSOD(DN vs64.7±3.8%)表达增高(均p0.05),尿8-OHdG排泄量(DNvs228.3±12.9ng/day,P0.05)减少。而与左卡尼汀低剂量组比较,高剂量组上述指标的改变更明显。与正常对照组相比DN组肾脏病理表现为肾小球硬化,足细胞数量减少及足突融合、基底膜增厚,ED-1阳性细胞数量增多,WT-1表达减少,与DN组比较左卡尼汀两组肾小球硬化程度减轻,足细胞数量增多,足突结构清楚,基底膜变薄,ED-1阳性细胞数减少,WT-1表达增多。结论:左卡尼汀对链脲霉素诱导的大鼠糖尿病肾病具有良好的保护作用,其机制可能与左卡尼汀抑制炎症,抗氧化及抑制凋亡相关。
[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.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2;R692.9

【参考文献】