葡萄籽原花青素對自發(fā)性高血壓大鼠腎臟結(jié)構(gòu)和泌尿功能的影響
本文選題:葡萄籽原花青素 + 自發(fā)性高血壓大鼠; 參考:《遵義醫(yī)學(xué)院》2016年碩士論文
【摘要】:目的:研究葡萄籽原花青素(GSP)對自發(fā)性高血壓大鼠(SHR)腎臟結(jié)構(gòu)和泌尿功能的影響并探討其可能機制。方法:8周齡雄性SHR 24只適應(yīng)性喂養(yǎng)1 w后隨機分成4組(n=6):SHR組(SHR)、GSP低劑量治療組(GSP-low,50 mg/kg)、GSP高劑量治療組(GSPhigh,200 mg/kg)和卡托普利陽性對照治療組(captopril,30 mg/kg);6只同齡雄性Wistar-Kyoto大鼠設(shè)為正常對照組(control)。按照實驗分組,給大鼠灌胃上述對應(yīng)劑量藥物及溶媒(2 ml/次/d),每2 w測量一次各組大鼠尾動脈收縮壓(SBP)。6 w后,用代謝籠收集各組大鼠24 h尿液,測定24 h尿蛋白、視黃醛結(jié)合蛋白(RBP)和α1微球蛋白(α1-MG)含量。摘眼球取血,收集血清,測定血尿素氮(BUN),血肌酐(SCr)及胱抑素C(Cys C)含量。摘取大鼠兩側(cè)腎臟,肉眼觀察腎臟大體形態(tài),稱量大鼠體重及左、右腎臟質(zhì)量,計算腎臟質(zhì)量指數(shù)(RMI)。HE和Masson染色下觀察腎臟組織形態(tài)和膠原含量變化并測定腎內(nèi)小動脈中膜與血管內(nèi)徑比值(MT/LD)、腎小球膠原纖維沉積評分(GCDS)及腎小管間質(zhì)病變評分(TIDS)。測定左腎皮質(zhì)中超氧化物歧化酶(SOD)和谷胱甘肽過氧化物酶(GSH-Px)活性、總抗氧化能力(T-AOC)及丙二醛(MDA)含量。蛋白免疫印跡法(Western blot)檢測腎皮質(zhì)中細胞外信號調(diào)節(jié)激酶1/2(ERK1/2)和磷酸化細胞外信號調(diào)節(jié)激酶1/2(p-ERK1/2)蛋白表達情況。結(jié)果:灌胃給藥6 w后,與control組比較,SHR組大鼠尾動脈SBP(2 w、4 w和6 w)、24 h尿蛋白、尿液中RBP和α1-MG含量、BUN、SCr、血清中Cys C含量、腎臟組織中膠原纖維、腎內(nèi)小動脈MT/LD、GCDS和TIDS、腎皮質(zhì)中MDA含量、ERK1/2和p-ERK1/2的蛋白表達均明顯升高(P0.01,P0.05),而腎皮質(zhì)中SOD、GSH-Px的活性和T-AOC均明顯降低(P0.05,P0.01);腎臟大體形態(tài)基本正常,兩側(cè)RWI均增大(P0.05),腎小球、腎間質(zhì)及腎小管均出現(xiàn)損傷性病理改變。與SHR組相比,GSP能顯著降低大鼠尾動脈SBP(2 w、4 w和6 w)、24h尿蛋白、尿液中RBP和α1-MG含量、BUN、SCr、血清中Cys C含量(P0.01,P0.05)、腎臟組織中膠原含量、MT/LD、GCDS和TIDS及腎皮質(zhì)中MDA含量、ERK1/2和p-ERK1/2的蛋白表達(P0.05,P0.01),升高腎皮質(zhì)中SOD、GSHPx的活性和T-AOC(P0.01),改善腎臟的病理損傷。以高劑量GSP治療組效果尤為顯著(P0.01),與captopril組療效相當(P0.05)。結(jié)論:GSP可以有效改善SHR腎臟結(jié)構(gòu)和泌尿功能的損傷,其機制與GSP具有降低SHR尾動脈SBP、提高SHR抗氧化應(yīng)激能力和減少腎臟組織中ERK1/2和pERK1/2的蛋白表達的作用有關(guān)。
[Abstract]:Aim: to study the effects of grape seed proanthocyanidin (GSP) on renal structure and urinary function in spontaneously hypertensive rats (SHR) and to explore its possible mechanism. Methods Twenty four male SHR (8 weeks old) were randomly divided into 4 groups after one week of adaptive feeding. They were randomly divided into 4 groups: the low dose group of SHRP GSP 50 mg 路kg ~ (-1) GSP) and captopriline 30 mg 路kg ~ (-1) 路kg ~ (-1) of captopriline 30 mg 路kg ~ (-1) 路kg ~ (-1) captopriline 30 mg 路kg ~ (-1) of captopriline 30 mg 路kg ~ (-1 / L) of captoprilium 30 mg 路kg ~ (-1 / L) of captopriline 30 mg 路kg ~ (-1) 路kg ~ (-1) ~ 6 male Wistar Kyoto rats of the same age. According to the experimental group, the rats were gavaged with the corresponding dose of the drug and the solvent for 2 ml/ times / d. The systolic blood pressure of the caudal artery of the rats in each group was measured every 2 weeks. The urine of the rats in each group was collected by metabolic cage for 24 hours, and the urine protein was measured at 24 hours. The contents of Retinal binding protein (RBP) and 偽 1 microglobulin (偽 1 MG). Blood samples were taken from eyeballs and serum samples were collected. The contents of blood urea nitrogen bun, serum creatinine (SCR) and cystatin (cystatin C) were determined. The bilateral kidneys of the rats were removed, the gross morphology of the kidneys was observed with the naked eye, the weight of the rats and the weight of the left and right kidneys were measured. RMI-HE and Masson staining were used to observe the changes of renal tissue morphology and collagen content, and to determine the ratio of membrane to vessel diameter of renal arterioles and the ratio of MTR / LDN, glomerular collagen fiber deposition score (GCDSs) and tubulointerstitial lesion score (TIDSN). The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and malondialdehyde (MDA) in left renal cortex were measured. Western blot was used to detect the expression of extracellular signal-regulated kinase 1 / 2 ERK1 / 2 and phosphorylated extracellular signal-regulated kinase 1 / 2 -ERK1 / 2 in renal cortex. Results: after 6 weeks, compared with the control group, the rats in the control group received 24 h urine protein, urinary RBP and 偽 1-MG, Cys C in serum and collagen fiber in the kidney. The expression of MDA in renal cortex, ERK1 / 2 and p-ERK1 / 2 increased significantly, while the activity of SODD-GSH-Px and T-AOC in renal cortex decreased P0.05P0.01. the renal morphology was basically normal, and the bilateral RWI was increased, glomeruli, glomeruli. Interstitial and tubulointerstitial pathological changes were observed. Compared with the SHR group, GSP could significantly decrease the urinary protein levels of SBP in the caudal artery of rats at 4 weeks and 6 weeks, respectively. The contents of RBP and 偽 1-MG in urine, the contents of Cys C in serum, and the contents of collagen in kidney and the protein expression of ERK1 / 2 and p-ERK1 / 2 in renal cortex and the protein expression of ERK1 / 2 and p-ERK1 / 2 in renal cortex were increased, and the activity of GSHPx and T-AOCP0.01in renal cortex were increased, and the pathological damage of kidney was improved. The effect of high dose GSP group was more significant than that of captopril group. ConclusionGSP can effectively improve the damage of renal structure and urinary function in SHR. The mechanism is related to the effect of GSP on decreasing SBP of SHR caudal artery, increasing the ability of anti-oxidative stress in SHR and decreasing the protein expression of ERK1 / 2 and pERK1 / 2 in renal tissue.
【學(xué)位授予單位】:遵義醫(yī)學(xué)院
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2016
【分類號】:R544.1
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