文献类型：期刊文献

中文题名：萆薢分清颗粒对单侧输尿管梗阻大鼠肾功能和Akt、TGF-β_(1)、GSK3β表达的影响

英文题名：Effects of Bixie Fenqing granules on expressions of Akt,TGF-β_(1)and GSK3βin renal fibrosis of rats with unilateral ureteral obstruction

作者：何彩苹[1];马鸿斌[2];魏锦慧[2];李根生[3];翟书玲[4];柳振华[2];张莲荷[2];马海兰[1]

第一作者：何彩苹

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730020;[3]安康市中医医院,陕西安康725000;[4]安阳市中医院,河南安阳455000

第一机构：甘肃中医药大学

年份：2025

卷号：34

期号：3

起止页码：293

中文期刊名：现代中西医结合杂志

外文期刊名：Modern Journal of Integrated Traditional Chinese and Western Medicine

基金：甘肃省名中医传承工作室建设项目(甘才社[2022]105号);甘肃省科技计划项目(21JR7RA577)。

语种：中文

中文关键词：单侧输尿管梗阻;萆薢分清颗粒;大鼠;肾纤维化;蛋白激酶B;转化生长因子-β_(1);糖原合成酶激酶3β

外文关键词：unilateral ureteral obstruction;Bixie Fenqing granules;rats;renal fibrosis;protein kinase B;transforming growth factor-β_(1);glycogen synthase kinase 3β

摘要：目的观察萆薢分清颗粒对单侧输尿管梗阻大鼠肾纤维化相关蛋白蛋白激酶B(Akt)、转化生长因子-β_(1)(TGF-β_(1))、糖原合成酶激酶3β(GSK3β)表达的影响,探讨萆薢分清颗粒的肾脏保护作用。方法取10只雄性SD大鼠作为正常组,另取50只雄性SD大鼠采用单侧输尿管梗阻的方法构建肾纤维化模型。将肾纤维化造模成功大鼠随机分为5组,每组10只。西药组给予2.62 mL/(kg·d)的氯沙坦钾片溶液灌胃,中药高、中、低剂量组分别给予13.12 mL/(kg·d)、6.56 mL/(kg·d)、3.28 mL/(kg·d)的萆薢分清颗粒溶液灌胃,正常组和模型组给予等量生理盐水灌胃,均1次/d,连续灌胃4周。实验过程中观察大鼠的一般状态,末次灌胃结束后留取血清、尿液及肾组织标本,检测血肌酐(SCr)、尿素氮(BUN)、尿微量白蛋白肌酐比值(ACR)、24 h尿蛋白定量(24h-UPQ),HE染色、Masson染色观察肾组织病理形态和胶原沉积情况,免疫组化法及Western blot法检测肾组织中Akt、TGF-β_(1)、GSK3β蛋白表达情况。结果与正常组比较,模型组大鼠精神萎靡,一般状态差,SCr、BUN水平和ACR、24h-UPQ均明显升高(P均<0.05);HE和Masson染色显示大鼠肾脏体积增大,结构紊乱,肾小球鲍曼囊囊腔增宽、小球萎缩,肾小管扩张,肾间质可见大量蓝色胶原纤维沉积,周围有空泡变性,组织结构较疏松;肾组织中Akt、TGF-β_(1)、GSK3β蛋白表达平均光密度值和蛋白相对表达量均明显升高(P均<0.05)。与模型组比较,各药物组大鼠情况均有不同程度改善,西药组、中药高剂量组改善最为明显;西药组、中药高剂量组SCr、BUN水平和ACR、24h-UPQ均明显降低(P均<0.05),HE和Masson染色显示肾脏病理变化均明显减轻,肾小球结构基本正常,仅见少量胶原纤维沉积,肾组织中Akt、TGF-β_(1)、GSK3β蛋白表达平均光密度值和蛋白相对表达量均明显降低(P均<0.05)。结论萆薢分清颗粒可通过下调Akt、TGF-β_(1)、GSK3β蛋白表达,保护单侧输尿管梗阻大鼠残存肾功能,减轻肾纤维化。
Objective It is to observe the effect of Bixie Fenqing granules on the expressions of fibrosis-associated proteins protein kinase B(Akt),transforming growth factor-β_(1)(TGF-β_(1)),and glycogen synthase kinase 3β(GSK3β)in rats with unilateral ureteral obstruction,and to explore the renoprotective effects of this medicine.Methods Sixty SPF male SD rats were selected,among which 10 rats were randomly selected as the blank group,and the other 50 rats were used to establish models of renal fibrosis by unilateral ureteral obstruction.The successful modeled rats were randomly divided into model group,western medicine group and high,medium and low dose groups of Chinese medicine,with 10 rats in each group.The high,medium and low dose groups of Chinese medicine were treated with 13.12 mL/(kg·d),6.56 mL/(kg·d)and 3.28 mL/(kg·d)of Bixie Fenqing granule solution by gavage,respectively,the western medicine group were given losartan potassium tablets solution 2.62 mL/(kg·d)by gavage,the blank group and model group were given the same amount of normal saline by gavage,all once daily,continuously gavaged for 4 weeks.The general state of the rats was observed during the experiment,the serum,urine and renal tissue samples were collected after the last gavage,then the levels of serum creatinine(SCr),blood urea nitrogen(BUN),urine microalbumin/creatinine(ACR)and 24-hour urinary protein quantification(24h-UPQ)were detected,the pathological changes of renal tissue were observed by HE and Masson staining,and the expressions of Akt,TGF-β_(1)and GSK3βin renal tissue were detected by immunohistochemistry and Western blot.Results Compared with the blank group,the rats in the model group were listless with poor general status,the levels of SCr,BUN,ACR and 24h-UPQ were obviously increased(all P<0.05);HE and Masson staining showed that the rat kidneys were enlarged in size and their structure were disorganized,the glomerular Bowman’s capsule cystic lumen was widened with atrophied glomeruli and dilated tubules,and a large number of blue collagen fibers were deposited in the renal interstitium,surrounded by vacuolar degeneration and with sparser tissue structure;the average optical density values and the relative protein expressions of Akt,TGF-β_(1),and GSK3βp in the renal tissues were all significantly increased(all P<0.05).Compared with the model group,the condition of rats in each treatment group was improved to varying degrees,and the improvements in the western medicine group and high dose group of Chinese medicine were the most obvious;the levels of SCr,BUN,ACR,and 24h-UPQ were significantly reduced in the western medicine group and high dose group of Chinese medicine(all P<0.05),HE and Masson staining showed that the pathological changes of the kidneys were significantly improved,the glomerular structure was basically normal,with only a small amount of deposited collagen fibers,and the average optical density values and the relative protein expressions of Akt,TGF-β_(1),and GSK3βp in the renal tissues were all significantly decreased(all P<0.05).Conclusion Bixie Fenqing granules can protect the residual renal function and attenuate renal fibrosis in rats with unilateral ureteral obstruction via down-regulating the protein expressions of Akt,TGF-β_(1)and GSK3β.