【摘要】：目的:采用鏈脲菌素(Streptozocin,STZ)誘導糖尿病大鼠模型,研究巨藻LN來源的巖藻多糖(Fucoidan,Fuc)對糖尿病大鼠護腎效果,并考察其護腎作用機制。方法:采用STZ誘導糖尿病大鼠模型,分為不經(jīng)STZ處理的Nor組(正常組,生理鹽水治療)及經(jīng)過STZ處理的Fuc-50(低劑量組,50mg/kg/d巖藻多糖治療)、Fuc-200(高劑量組,200mg/kg/d巖藻多糖治療)、Cap(陽性對照組,卡托普利治療)及Mod(模型組,生理鹽水治療)五個實驗組。采用全自動生化分析儀檢測尿素氮(Urea nitrogen,UREA)、尿微量總蛋白(Micro total protein,M-TP)、高密度脂蛋白膽固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白膽固醇(Low density lipoprotein cholesterol,LDL-C)、血清肌酐酸(Creatinine acid,CREA)、膽固醇(Cholesterol,CHOL)、血糖(Glucose,GLU)、甘油三酯(Triglyceride,TRIG)、及糖化血清蛋白(FRUC);采用Elisa法檢測24 h尿樣中尿肌酸酐(Urinary creatinine,u Cr)、尿白蛋白(Urinary albumin,u Alb)及腎臟P-選擇素、α-腫瘤壞死因子(Tumor necrosis factor-α,TNF-α)、白細胞介素-6(Interleukin-6,IL-6)及絲裂原激活的蛋白激酶/MAP激酶(MAPK)的表達量;蘇木精-伊紅染色(Hematoxylin-eosin staining,HE)考察大鼠腎臟病變情況;免疫組化法測定腎臟P-選擇素及IL-6、β-生長轉(zhuǎn)化因子(Transforming growth factor,TGF-β)的表達情況;RT-PCR檢測P-選擇素及選擇素相關的細胞間黏附分子-1(Intercelluar adhesion molecule-1,ICAM-1)、IL-6和TGF-β的m RNA轉(zhuǎn)錄水平。結(jié)果:(1)巖藻多糖能夠使實驗鼠糖尿病腎病(Diabetic nephropathy,DN)發(fā)展期間體重基本維持穩(wěn)定,減輕糖尿病鼠的體重下降。Fuc-50及Fuc-200巖藻多糖治療組與Mod組相比,巖藻多糖能夠減少DN大鼠排尿量,尤其是高劑量Fuc-200組,可在一定程度上抑制糖尿病大鼠DN的發(fā)展及惡化。(2)與Nor組相比,糖尿病模型大鼠24 h尿樣中,u Alb及M-TP出現(xiàn)顯著升高。服用巖藻多糖可以顯著降低尿液M-TP、UREA、u Alb以及血液中FRUC等多項生化指標,降低DN大鼠蛋白尿發(fā)生幾率,維持和保護腎小球基本結(jié)構(gòu)及功能,減輕糖尿病導致的腎臟損傷,進而抑制糖尿病腎病的發(fā)展。(3)HE結(jié)果顯示,巖藻多糖能夠維持糖尿病大鼠腎臟正常生理結(jié)構(gòu),減輕炎癥反應、減小炎癥細胞浸潤面積。Fuc-50及Fuc-200巖藻多糖治療組實驗大鼠腎臟P-選擇素及選擇素依賴的炎癥因子在m RNA及蛋白水平均出現(xiàn)顯著下調(diào),表明巖藻多糖可以緩解P-選擇素及炎癥因子介導的炎癥反應,從而對糖尿病大鼠的腎臟功能發(fā)揮保護作用。結(jié)論:巖藻多糖可以緩解糖尿病大鼠所出現(xiàn)的多尿、體重減少及腎功能損傷等典型糖尿病及糖尿病腎病癥狀,降低尿液及血液各項生化指標,更好的保護并修復腎小球正常生理結(jié)構(gòu),緩解P-選擇素及炎癥因子介導的炎癥反應,減小炎癥細胞浸潤面積,減緩糖尿病腎病病情的發(fā)展,是一種用于治療糖尿病腎病的潛在藥物。
[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, 偽 -tumor necrosis factor (Tumor necrosis factor- 偽 (TNF- 偽) 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.
【學位授予單位】：大連醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R285.5

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