目的 探究澤瀉多糖對(duì)糖尿病大鼠腎損傷的改善作用。方法 SPF級(jí)SD雄性大鼠隨機(jī)分為對(duì)照組，模型組，吡格列酮［過(guò)氧化物酶體增殖物激活受體γ（PPAR-γ）激活劑，20 mg·kg^-1］組，澤瀉多糖低、中、高劑量（100、200、400 mg·kg^-1）組和澤瀉多糖（400 mg·kg^-1）＋ GW9662（PPAR-γ抑制劑，10 mg·kg^-1）組，除對(duì)照組外均采用高糖高脂＋鏈脲佐菌素（STZ）檸檬酸鈉緩沖液法制備糖尿病腎?。―N）大鼠模型，造模后各組ig給藥，每天1次，連續(xù)6周。血糖儀測(cè)定大鼠空腹血糖（FBG）水平；全自動(dòng)生化分析儀檢測(cè)大鼠血清肌酐、尿酸、尿素氮水平，檢測(cè)24 h尿蛋白及尿肌酐，計(jì)算內(nèi)生肌酐清除率（Ccr）；處死大鼠，計(jì)算大鼠腎臟指數(shù)；HE染色觀察大鼠右側(cè)腎臟組織病理學(xué)變化；Western blotting法檢測(cè)腎臟組織PPAR-γ/肝X受體-α（LXR-α）/ATP結(jié)合盒轉(zhuǎn)運(yùn)蛋白G1（ABCG1）、腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-1β（IL-1β）蛋白水平。結(jié)果 與對(duì)照組比較，模型組大鼠毛色枯黃，體質(zhì)量顯著減輕（P<0.05）；腎小球細(xì)胞空泡化、腎小球基底膜增厚；腎臟指數(shù)、FBG、24 h尿蛋白、尿酸、尿素氮、TNF-α和IL-1β蛋白水平顯著升高（P<0.05），Ccr和PPAR-γ、LXR-α、ABCG1蛋白水平顯著降低（P<0.05）；與模型組比較，吡格列酮組和中、高劑量澤瀉多糖組大鼠毛色及飲食、飲水逐漸恢復(fù)，體質(zhì)量顯著增加（P<0.05）；腎損傷程度減輕；FBG、24 h尿蛋白、尿酸、TNF-α和IL-1β蛋白水平顯著降低（P<0.05），Ccr及PPAR-γ、LXR-α、ABCG1蛋白水平顯著升高（P<0.05）；澤瀉多糖高劑量組腎臟指數(shù)顯著降低（P<0.05）。高劑量澤瀉多糖組與吡格列酮組各指標(biāo)差異比較無(wú)統(tǒng)計(jì)學(xué)意義，GW9662可逆轉(zhuǎn)高劑量澤瀉多糖對(duì)大鼠腎臟功能的保護(hù)作用。結(jié)論 澤瀉多糖可能通過(guò)激活PPAR-γ/LXR-α/ABCG1通路保護(hù)DN大鼠腎臟。

Objective To explore the ameliorative effect of Alisma orientalis polysaccharide (AOP) on renal injury in diabetes rats. Methods Fifty SPF male SD rats were randomly divided into control group, model group and pioglitazone group (PPAR-γ activator, 20 mg·kg^-1), AOP low, medium and high dose (100, 200, and 400 mg·kg^-1) group, AOP high dose (400 mg·kg^-1) + GW9662 (PPAR-γ inhibitor, 10 mg·kg^-1) group, except the control group, DM rat models were made by high glucose and high fat + streptozotocin (STZ) sodium citrate buffer method. After modeling, each group was administered ig once a day for six consecutive weeks. After administration, serum fasting blood glucose (FBG), serum creatinine, uric acid and urea nitrogen were measured by fully automatic biochemical analyzer. The levels of 24-hour urinary protein and urinary creatinine were measured, and the endogenous creatinine clearance rate (CCR) was calculated. The rats were sacrificed and the renal index was calculated. The histopathological changes of the right kidney were observed by HE staining. Renal peroxisome proliferator activated receptor γ (PPAR-γ)/liver X receptor-α (LXR-α)/ATP binding cassette transporter G1 (ABCG1), TNF-α, IL-1β protein level was detected by Western blotting. Results Compared with the control group, the model group had withered and yellow hair, reduced body weight (P < 0.05), vacuolization of glomerular cells, thickening of glomerular basement membrane, renal index, FBG, 24-h urinary protein, uric acid, urea nitrogen and the protein level of TNF-α and IL-1β increased (P < 0.05), CCR and the protein level of PPAR-γ, LXR-α, ABCG1 decreased (P < 0.05). Compared with model group, the hair color, diet and drinking water of pioglitazone group, medium and high dose AOP group gradually recovered, the body weight increased (P < 0.05), the degree of renal injury decreased, FBG, 24-h urinary protein, uric acid and the protein level of TNF-α and IL-1β decreased (P < 0.05), CCR and PPAR-γ, LXR-α, and ABCG1 protein level increased (P < 0.05), the kidney index of the high-dose group of AOP significantly decreased (P < 0.05). and there was no significant difference between high-dose AOP group and pioglitazone group. GW9662 could reverse the protective effect of AOP on renal function in rats. Conclusion AOP may protect the renal function of DN rats by promoting the activation of PPAR-γ/LXR-α/ABCG1 pathway.

R285.5；R587.1

國(guó)家自然科學(xué)基金資助項(xiàng)目（81904190）