巨藻LN岩藻多糖对糖尿病大鼠护肾功效机理的研究
发布时间：2018-12-19 17:01
【摘要】：目的:采用链脲菌素(Streptozocin,STZ)诱导糖尿病大鼠模型,研究巨藻LN来源的岩藻多糖(Fucoidan,Fuc)对糖尿病大鼠护肾效果,并考察其护肾作用机制。方法:采用STZ诱导糖尿病大鼠模型,分为不经STZ处理的Nor组(正常组,生理盐水治疗)及经过STZ处理的Fuc-50(低剂量组,50mg/kg/d岩藻多糖治疗)、Fuc-200(高剂量组,200mg/kg/d岩藻多糖治疗)、Cap(阳性对照组,卡托普利治疗)及Mod(模型组,生理盐水治疗)五个实验组。采用全自动生化分析仪检测尿素氮(Urea nitrogen,UREA)、尿微量总蛋白(Micro total protein,M-TP)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-C)、血清肌酐酸(Creatinine acid,CREA)、胆固醇(Cholesterol,CHOL)、血糖(Glucose,GLU)、甘油三酯(Triglyceride,TRIG)、及糖化血清蛋白(FRUC);采用Elisa法检测24 h尿样中尿肌酸酐(Urinary creatinine,u Cr)、尿白蛋白(Urinary albumin,u Alb)及肾脏P-选择素、α-肿瘤坏死因子(Tumor necrosis factor-α,TNF-α)、白细胞介素-6(Interleukin-6,IL-6)及丝裂原激活的蛋白激酶/MAP激酶(MAPK)的表达量;苏木精-伊红染色(Hematoxylin-eosin staining,HE)考察大鼠肾脏病变情况;免疫组化法测定肾脏P-选择素及IL-6、β-生长转化因子(Transforming growth factor,TGF-β)的表达情况;RT-PCR检测P-选择素及选择素相关的细胞间黏附分子-1(Intercelluar adhesion molecule-1,ICAM-1)、IL-6和TGF-β的m RNA转录水平。结果:(1)岩藻多糖能够使实验鼠糖尿病肾病(Diabetic nephropathy,DN)发展期间体重基本维持稳定,减轻糖尿病鼠的体重下降。Fuc-50及Fuc-200岩藻多糖治疗组与Mod组相比,岩藻多糖能够减少DN大鼠排尿量,尤其是高剂量Fuc-200组,可在一定程度上抑制糖尿病大鼠DN的发展及恶化。(2)与Nor组相比,糖尿病模型大鼠24 h尿样中,u Alb及M-TP出现显著升高。服用岩藻多糖可以显著降低尿液M-TP、UREA、u Alb以及血液中FRUC等多项生化指标,降低DN大鼠蛋白尿发生几率,维持和保护肾小球基本结构及功能,减轻糖尿病导致的肾脏损伤,进而抑制糖尿病肾病的发展。(3)HE结果显示,岩藻多糖能够维持糖尿病大鼠肾脏正常生理结构,减轻炎症反应、减小炎症细胞浸润面积。Fuc-50及Fuc-200岩藻多糖治疗组实验大鼠肾脏P-选择素及选择素依赖的炎症因子在m RNA及蛋白水平均出现显著下调,表明岩藻多糖可以缓解P-选择素及炎症因子介导的炎症反应,从而对糖尿病大鼠的肾脏功能发挥保护作用。结论:岩藻多糖可以缓解糖尿病大鼠所出现的多尿、体重减少及肾功能损伤等典型糖尿病及糖尿病肾病症状,降低尿液及血液各项生化指标,更好的保护并修复肾小球正常生理结构,缓解P-选择素及炎症因子介导的炎症反应,减小炎症细胞浸润面积,减缓糖尿病肾病病情的发展,是一种用于治疗糖尿病肾病的潜在药物。
[Abstract]:Aim: to study the effects of fucoidan polysaccharide (Fucoidan,Fuc) derived from macroalgae LN on the renal protection of diabetic rats induced by streptozotocin (Streptozocin,STZ) and its mechanism. Methods: STZ induced diabetic rats were divided into three groups: Nor group (normal group, normal saline group), Fuc-50 (low dose group, 50mg/kg/d fucose treatment group) and Fuc-200 (high dose group) treated with STZ. 200mg/kg/d fucoidan was used to treat), Cap (positive control group, captopril treatment and Mod (model group, normal saline treatment). Determination of urea nitrogen (Urea nitrogen,UREA), urinary trace total protein (Micro total protein,M-TP), high density lipoprotein cholesterol (High density lipoprotein cholesterol,HDL-C), low density lipoprotein cholesterol (Low density lipoprotein cholesterol,) by automatic biochemical analyzer LDL-C, serum creatinine (Creatinine acid,CREA), cholesterol (Cholesterol,CHOL), blood glucose (Glucose,GLU), triglyceride (Triglyceride,TRIG), and glycosylated serum protein (FRUC); Determination of urinary creatinine (Urinary albumin,u Alb), renal P-selectin, 伪 -tumor necrosis factor (Tumor necrosis factor- 伪 (TNF- 伪) and interleukin-6 (Interleukin-6,) in 24 h urine samples by Elisa assay IL-6) and the expression of mitogen-activated protein kinase / MAP kinase (MAPK); Hematoxylin-eosin staining (Hematoxylin-eosin staining,HE) was used to investigate the renal lesions in rats, and the expression of P- selectin and IL-6, 尾-growth transforming factor (Transforming growth factor,TGF- 尾) in the kidney were detected by immunohistochemistry. RT-PCR was used to detect the m RNA transcription levels of P- selectin and selectin-related intercellular adhesion molecule-1 (Intercelluar adhesion molecule-1,ICAM-1, IL-6 and TGF- 尾. Results: (1) fucoidan could keep the weight stable during the development of diabetic nephropathy (Diabetic nephropathy,DN) and reduce the weight loss of diabetic rats. Fucoidan could reduce urination in DN rats, especially in high dose Fuc-200 group, which could inhibit the development and deterioration of DN in diabetic rats to some extent. (2) compared with Nor group, 24 h urine samples of diabetic rats were observed. U Alb and M-TP increased significantly. Taking fucoidan could significantly reduce urine M-TPN urEAU Alb and FRUC in blood, decrease the probability of proteinuria in DN rats, and maintain and protect the basic structure and function of glomeruli. (3) the results of HE showed that fucoidan could maintain the normal physiological structure of kidney and alleviate inflammation in diabetic rats. Decrease the area of inflammatory cell infiltration. The levels of P- selectin and selectin dependent inflammatory factors in kidney of Fuc-50 and Fuc-200 treated rats were significantly decreased at the level of m RNA and protein. These results suggest that fucoidan can alleviate the inflammatory response mediated by P- selectin and inflammatory factors and thus play a protective role in renal function of diabetic rats. Conclusion: fucoidan can relieve the symptoms of diabetes mellitus and diabetic nephropathy such as polyuria, weight loss and renal function injury, and decrease the biochemical indexes of urine and blood in diabetic rats. To better protect and repair the normal physiological structure of glomeruli, alleviate the inflammatory response mediated by P- selectin and inflammatory factors, reduce the area of inflammatory cell infiltration, and slow the development of diabetic nephropathy. Is a potential drug for the treatment of diabetic nephropathy.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5
本文编号：2387205
[Abstract]:Aim: to study the effects of fucoidan polysaccharide (Fucoidan,Fuc) derived from macroalgae LN on the renal protection of diabetic rats induced by streptozotocin (Streptozocin,STZ) and its mechanism. Methods: STZ induced diabetic rats were divided into three groups: Nor group (normal group, normal saline group), Fuc-50 (low dose group, 50mg/kg/d fucose treatment group) and Fuc-200 (high dose group) treated with STZ. 200mg/kg/d fucoidan was used to treat), Cap (positive control group, captopril treatment and Mod (model group, normal saline treatment). Determination of urea nitrogen (Urea nitrogen,UREA), urinary trace total protein (Micro total protein,M-TP), high density lipoprotein cholesterol (High density lipoprotein cholesterol,HDL-C), low density lipoprotein cholesterol (Low density lipoprotein cholesterol,) by automatic biochemical analyzer LDL-C, serum creatinine (Creatinine acid,CREA), cholesterol (Cholesterol,CHOL), blood glucose (Glucose,GLU), triglyceride (Triglyceride,TRIG), and glycosylated serum protein (FRUC); Determination of urinary creatinine (Urinary albumin,u Alb), renal P-selectin, 伪 -tumor necrosis factor (Tumor necrosis factor- 伪 (TNF- 伪) and interleukin-6 (Interleukin-6,) in 24 h urine samples by Elisa assay IL-6) and the expression of mitogen-activated protein kinase / MAP kinase (MAPK); Hematoxylin-eosin staining (Hematoxylin-eosin staining,HE) was used to investigate the renal lesions in rats, and the expression of P- selectin and IL-6, 尾-growth transforming factor (Transforming growth factor,TGF- 尾) in the kidney were detected by immunohistochemistry. RT-PCR was used to detect the m RNA transcription levels of P- selectin and selectin-related intercellular adhesion molecule-1 (Intercelluar adhesion molecule-1,ICAM-1, IL-6 and TGF- 尾. Results: (1) fucoidan could keep the weight stable during the development of diabetic nephropathy (Diabetic nephropathy,DN) and reduce the weight loss of diabetic rats. Fucoidan could reduce urination in DN rats, especially in high dose Fuc-200 group, which could inhibit the development and deterioration of DN in diabetic rats to some extent. (2) compared with Nor group, 24 h urine samples of diabetic rats were observed. U Alb and M-TP increased significantly. Taking fucoidan could significantly reduce urine M-TPN urEAU Alb and FRUC in blood, decrease the probability of proteinuria in DN rats, and maintain and protect the basic structure and function of glomeruli. (3) the results of HE showed that fucoidan could maintain the normal physiological structure of kidney and alleviate inflammation in diabetic rats. Decrease the area of inflammatory cell infiltration. The levels of P- selectin and selectin dependent inflammatory factors in kidney of Fuc-50 and Fuc-200 treated rats were significantly decreased at the level of m RNA and protein. These results suggest that fucoidan can alleviate the inflammatory response mediated by P- selectin and inflammatory factors and thus play a protective role in renal function of diabetic rats. Conclusion: fucoidan can relieve the symptoms of diabetes mellitus and diabetic nephropathy such as polyuria, weight loss and renal function injury, and decrease the biochemical indexes of urine and blood in diabetic rats. To better protect and repair the normal physiological structure of glomeruli, alleviate the inflammatory response mediated by P- selectin and inflammatory factors, reduce the area of inflammatory cell infiltration, and slow the development of diabetic nephropathy. Is a potential drug for the treatment of diabetic nephropathy.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R285.5
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