益智仁提取物对糖尿病肾病模型小鼠的疗效及机制研究  

Effect of extract by mineral ether from Alpinia oxyphyllae on diabetic nephropathy mice and its mechanism

作　　者：刘嫱[1] 房磊臣 韦祎[1] 高新征[1] 刘一鸣[1] 谢毅强[1] 

机构地区：[1]海南医学院药理教研室,海南海口571101 [2]广东省深圳市武警医院生殖中心,广东深圳518032

出　　处：《中国医药导报》2015年第33期21-25,共5页China Medical Herald

基　　金：国家自然科学基金资助项目(8147318;81360586);海南省自然科学基金项目(812186;814290);海口市重点科技计划项目(2012-076);海南医学院科研培育基金项目(HY 2012-009)

摘　　要：目的探讨益智仁提取物对糖尿病肾病(DN)模型小鼠的疗效及可能机制。方法 48只雄性昆明小鼠,分为正常对照组,DN模型组,阳性药物组,益智仁提取物高、中、低剂量组,每组各8只。给予小鼠1次大剂量腹腔注射链脲佐菌素(150 mg/kg),进行DN造模,成模后,正常对照组给予灌胃蒸馏水10 m L/(kg·d),阳性药物组给予厄贝沙坦10 mg/kg灌胃,益智仁提取物高、中、低剂量组给予益智仁提取物石油醚部位20、10、5 g/(kg·d)灌胃,连续4周。定期观察血糖、尿蛋白、肾功能[血尿素氮(BUN)、肌酐(Scr)],实验结束时,处死小鼠,测定相对肾重,肾组织做病理形态学检查,免疫组化检测水通道蛋白2(AQP2)。结果成模小鼠随着实验进行,表现出高血糖,并出现蛋白尿,肾功能受到损害,血肌酐明显上升,病理检查发现肾小球明显肥大,系膜区扩张,基膜增厚。药物干预4周后,与DN模型组比较,益智仁提取物各剂量组的24 h尿蛋白定量明显降低,差异有高度统计学意义(P<0.01);益智仁提取物各剂量组BUN、Scr水平也明显降低,差异有高度统计学意义(P<0.01)。HE染色结果显示益智仁提取物高剂量组的病理改变明显减轻。免疫组化结果显示正常对照组AQP2无阳性表达,DN模型组AQP2阳性表达,益智仁提取物高剂量组AQP2的阳性表达减弱。结论益智仁提取物(石油醚部位)可以明显改善小鼠糖尿病肾病的损害,一定程度的保护肾功能,延缓肾功能减退。AQP2的表达下调可能是该物质对抗糖尿病肾病的作用机制。Objective To study the effect and mechanism of Alpinia oxyphyllae extract on diabetic nephropathy （DN） mice model. Methods 48 KM mice were were divided into 6 groups： DN model group, normal control group, positive control group, Alpinia oxyphyllae extract low, middle, high dosage group, with 8 mice in each group. DN model was in- duced by peritoneal injection of streptozotocin （STZ） 150 mg/kg, after successfully established model, normal control group was given distilled water 10 mL/（kg.d） gavage, DN model group was given Irbesartan 10 mg/kg gavage, Alpinia oxyphyllae extract low, middle, high dosage group were given Alpinia oxyphyllae extract by mineral ether 5,10, 20 g/ （kg.d）, for 4 weeks. Bloood glucose, urine protein, renal function （BUN, Scr） were observed periodicly, when the experiment finished, mice were killed, relative kidney weight was measured, kidney tissue was observed by histomorphology,AQP2 was detected by immunohistochemistry. Results Hyperglycemia, urinary protein, damaged renal function, and increased serum creatinine were observed in model mice, pathological examination Showed that glomerular hypertrophy, mesangial expansion, and basement mem- brane thickening. After giving drugs 4 weeks, compared with DN model group, 24 h urinary protein in Alpinia oxyphyllae extract low, middle, high dosage group reduced significantly, the differences were statistically significant （P 〈 0.01）; BUN, Scr in Alpinia oxyphyllae extract low, middle, high dosage group reduced significantly, the differences were statistically significant （P 〈 0.01）. The results of HE staining showed that pathologic change obviously alleviated in in A lpinia oxyphyllae extract high dosage group. The results of immunohistochemistry showed that AQP2 in normal control group had no positive expression, AQP2 in DN model group had positive expression, AQP2 in Alpinia oxyphyllae extract high dosage group had weak positive expres- sion. Conclusion Alpinia oxyphyllae extract by mineral ether can protect the

关 键 词：益智仁提取物 糖尿病肾病 水通道蛋白2 

分 类 号：R587.1[医药卫生—内分泌]