复方降糖玉液调节JAK2/STAT3/SOCS-1通路对糖尿病肾损伤大鼠的保护作用研究  

Protective effect of Compound Jiangtang Yuye on diabetic kidney injury rats by regulating JAK2/STAT3/SOCS-1 pathway

作　　者：古丽努尔·艾尼 刘春丽[1] 王彦娥 Gulinuer Aini;LIU Chunli;WANG Yan’e(The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,Xinjiang,China)

机构地区：[1]新疆医科大学第一附属医院,新疆乌鲁木齐830054

出　　处：《现代中西医结合杂志》2023年第18期2497-2503,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：新疆维吾尔自治区自然科学基金资助项目(2022D01C317)。

摘　　要：目的基于酪氨酸蛋白激酶2(JAK2)/信号传导及转录激活因子3(STAT3)/细胞因子信号抑制物1(SOCS-1)通路研究复方降糖玉液对糖尿病肾损伤大鼠的保护作用机制。方法随机从72只雄性SD大鼠中取12只作为空白组,其余大鼠采用高糖高脂饲料联合链脲佐菌素(STZ)法建立糖尿病肾损伤模型。将造模成功大鼠随机分为模型组、厄贝沙坦组及复方降糖玉液低、中、高剂量组,每组12只。复方降糖玉液低、中、高剂量组分别给予2.5 g/kg、5 g/kg、10 g/kg(以生药含量计)复方降糖玉液灌胃,厄贝沙坦组给予厄贝沙坦15 mg/kg灌胃,均1次/d,连续灌胃8周。收集24 h尿液测定24 h尿蛋白定量,尾静脉取血测定空腹血糖水平,腹主动脉取血测定糖化血红蛋白、尿素氮(BUN)、血肌酐(SCr)水平,取肾组织计算肾指数,ELISA法测定肾组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、单核细胞趋化蛋白-1(MCP-1)含量,HE染色法观察肾组织病理学形态,TUNEL染色法测定肾组织细胞凋亡率,Western blot法测定肾组织中p-JAK2、JAK2、p-STAT3、STAT3及SOCS-1蛋白表达情况。结果与空白组比较,模型组大鼠24 h尿蛋白定量、空腹血糖、糖化血红蛋白、BUN、SCr、肾指数、肾组织细胞凋亡率及肾组织中TNF-α、IL-1β、MCP-1含量和p-JAK2/JAK2、p-STAT3/STAT3比值均明显升高(P均<0.05),肾组织中SOCS-1蛋白相对表达量明显降低(P<0.05),肾组织炎症浸润、肾小管扩张;与模型组比较,复方降糖玉液各组及厄贝沙坦组大鼠24 h尿蛋白定量、空腹血糖、糖化血红蛋白、BUN、SCr、肾指数、肾组织细胞凋亡率及肾组织中TNF-α、IL-1β、MCP-1含量和p-JAK2/JAK2、p-STAT3/STAT3比值均明显降低(P均<0.05),肾组织中SOCS-1蛋白相对表达量均明显升高(P均<0.05),肾组织炎症浸润明显减轻,且各项指标随着复方降糖玉液剂量的增加变化更明显。结论复方降糖玉液能够有效控制糖尿病肾损�Objective It is to investigate the mechanism of protective effect of Compound Jiangtang Yuye(CJY)on diabetic renal injury in rats via tyrosine protein kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)/suppressor of cytokine signaling 1(SOCS-1)pathway.Methods Seventy-two male SD rats were randomly selected,in which 12 rats were selected as the blank group,and the rest of the rats were used to establish diabetic kidney injury models by high sugar and fat chow combined with streptozotocin(STZ)by intraperitoneal injection.The successfully modeled rats were randomly divided into model group,irbesartan group,and low,medium,and high dose groups of CJY,with 12 rats in each group.The low,medium and high dose groups of CJY were given CJY(according to crude drug content)2.5 g/kg,5 g/kg and 10 g/kg by gavage,respectively,and the irbesartan group was given irbesartan 15 mg/kg by gavage,all once daily,continuously treated for 8 weeks.The 24 h urine was collected to determine the 24 h urine protein quantification,the blood was taken from the tail vein to determine the level of fasting blood glucose,the blood from the abdominal aorta was taken to determine the levels of glycosylated hemoglobin,blood urea nitrogen(BUN),and serum creatinine(SCr),the renal tissue was taken to calculate the renal index,the contents of tumor necrosis factor-ɑ(TNF-ɑ),interleukin-1β(IL-1β),and monocyte chemotactic protein-1(MCP-1)in renal tissue were detected by ELISA,the pathological morphology of renal tissues was observed by HE staining,the apoptosis rate of renal tissues was detected by TUNEL staining,and the expressions of p-JAK2,JAK2,p-STAT3,STAT3,and SOCS-1 proteins in renal tissues were detected by Western blot.Results Compared with the blank group,the levels of 24 h urine protein quantification,fasting blood glucose,glycosylated hemoglobin,BUN,SCr,renal index,renal tissue apoptosis rate,and the contents of TNF-ɑ,IL-1β,and MCP-1 in renal tissues,and the ratios of p-JAK2/JAK2,and p-STAT3/STAT3 of rats in the model gr

关 键 词：糖尿病肾损伤 复方降糖玉液 酪氨酸蛋白激酶2 信号传导及转录激活因子3 细胞因子信号抑制物1 

分 类 号：R-332[医药卫生]