摘要
目的探讨丹红注射液对糖尿病肾病(DKD)大鼠的保护作用及其潜在机制。方法使用单侧肾脏切除术,高脂饮食和链脲佐菌素诱导Sprague-Dawley大鼠发生DKD。选取3只单侧肾脏切除术和高脂饮食处理的大鼠作为正常对照组(NM组,n=3),模型建立成功后将大鼠分为丹红注射液组(DH组,n=4)和生理盐水注射组(NS组,n=3)。DH组大鼠每天腹腔注射丹红注射液(2mL/kg,2周),NS组和NM组大鼠每天腹腔注射生理盐水(2mL/kg,2周)。在给药后第10周后收集大鼠的尿液,麻醉处死大鼠后收集其血清和肾脏。全自动生化分析仪检测大鼠的肾功能和血脂水平,制备超薄切片进行肾脏病理染色,微阵列检测差异表达基因。结果与NS组比较,DH组的血肌酐(Scr)、胱抑素C(Cys-C)、24h尿总蛋白(24hTP)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)降低,而高密度脂蛋白胆固醇(HDL-C)升高(P<0.05)。HE染色显示,丹红注射液可以减轻DKD大鼠的肾脏病理损伤。微阵列共筛选出464个差异表达基因,其中包括185个上调基因和279个下调基因。KEGG通路富集分析表明,与NS组相比,过氧化物酶体增殖物激活受体(PPAR)信号通路、脂肪细胞因子信号通路及脂肪的消化和吸收3条通路在DH组明显上调,而初级胆汁酸生物合成和胆汁合成2条通路在DH组明显下调。5条通路涉及的主要基因包括ACSBG1、ADIPOQ、FABP4、SLC27A5、ABCA1和CYP8B1。STEM趋势分析差异表达的mRNA聚类有7个趋势明显。GO分析显示,差异表达基因的功能与对糖尿病的发生、发展至关重要的生物学过程有关。免疫组织化学染色显示PPAR信号通路关键基因PPARγ在NS组表达明显低于NM组,而使用丹红注射液处理后PPARγ表达相比NS组明显升高。结论丹红注射液能够改善DKD大鼠的肾功能和病理损伤,明显改变其基因表达谱,且此作用与脂代谢通路有关。
Objective To investigate the protective effect of Danhong Injection on the rats with diabetic kidney disease(DKD)and its underlying mechanism.Methods Unilateral nephrectomy,high-fat diet,and streptozotocin were used to induce DKD in Sprague-Dawley rats.Three rats with unilateral nephrectomy and high-fat diet treatment were selected as the normal control group(NM,n=3).After the model was successfully established,the rats were divided into the Danhong Injection group(DH,n=4)and saline injection group(NS,n=3).The rats in the DH group were intraperitoneally injected with Danhong Injection daily(2 mL/kg,2 weeks),and the rats in the NS and NM group were intraperitoneally injected with saline daily(2 mL/kg,2 weeks).The urine was collected at 10 week after medication,and the serum and kidneys were collected after the rats were anesthetized and sacrificed.The automatic biochemical analyzer was used to detect the renal function and blood lipid levels of rats.Ultrathin sections were prepared for conducting renal pathological staining.Differentially expressed genes were detected by microarray.Results Compared with the NS group,serum creatinine(Scr),cystatin C(Cys-C),24-h total protein(24 hTP),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)in the DH group decreased,while the high-density lipoprotein cholesterol(HDL-C)level increased.The HE staining showed that Danhong Injection could alleviate renal pathological damage in DKD rats.A total of 464 differentially expressed genes were screened out by the microarray,including 185 up-regulated genes and 279 down-regulated genes.The KEGG pathway enrichment analysis showed that the peroxisome proliferator-activated receptor(PPAR)signaling pathway,adipocytokine signaling pathway,and the fat digestion and absorption pathways were significantly up-regulated in the DH group compared to the NS group,while primary biliary acid biosynthesis and bile synthesis pathways were significantly down-regulated in the DH group.The major genes involved in the five pathways include
作者
杨雪
肖祥
李怡
钟翔
王莉
李贵森
YANG Xue;XIAO Xiang;LI Yi;ZHONG Xiang;WANG Li;LI Guisen(Clinical Medical College Southwest Medical University,Luzhou, Sichuan 646000;Department of Nephrology,Sichuan Academy of Medical Sciences/Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China)
出处
《重庆医学》
CAS
2019年第13期2161-2166,共6页
Chongqing medicine
基金
国家自然科学基金项目(81300618)
四川省科技青年创新团队项目(2015TD0013)
关键词
糖尿病肾病
丹红注射液
脂代谢障碍
diabetic nephropathies
Danhong Injection
lipid metabolism disorders
