通腑泄浊法对慢性肾脏病大鼠TGF-β1/p38MAPK信号通路的调节作用
|
摘要
目的考察通腑泄浊法对慢性肾脏病大鼠TGF-β1/p38MAPK信号通路的调节作用。方法 30只大鼠随机分为空白组、模型组、通腑泄浊法组、大黄配方颗粒组,灌胃给予2.5%腺嘌呤混悬液(200 mg/kg)建立慢性肾脏病大鼠模型。8周给药后,检测肾功能指标、肾脏病理变化、24 h尿蛋白、尿毒症毒素、TGF-β1/p38MAPK信号通路、肾脏纤维化程度。结果与模型组比较,通腑泄浊法组尿素氮(BUN)、血肌酐(Scr)、胱抑素(CysC)、同型半胱氨酸(HCY)、硫酸吲哚酚(IS)、24 h尿蛋白、IL-6、TGF-β1水平,α-SMA、TGF-β1、p-p38MAPK蛋白表达,肾脏纤维化程度显著降低(P<0.05,P<0.01)。结论通腑泄浊法可通过减少尿毒症毒素、抑制被活化的TGF-β1/p38MAPK信号通路来延缓慢性肾脏病大鼠肾纤维化进展。
AIM To investigate the regulatory effects of Discharging Fu-organ and Removing Turbidity Method on TGF-β1/p38 MAPK signaling pathway in chronic kidney disease rats.METHODS Thirty rats were randomly divided into blank group, model group, Discharging Fu-organ and Removing Turbidity Method group and Dahuang Formula Granules group. The rat model for chronic kidney disease was established by intragastric administration of 2.5% adenine suspension(200 mg/kg). After 8-week administration, renal function indices, renal pathological changes, 24 h urinary protein, uremic toxins, TGF-β1/p38 MAPK signaling pathway and renal fibrosis degree were detected.RESULTS Compared with the model group, the Discharging Fu-organ and Removing Turbidity Method group demonstrated significantly decreased BUN, Scr, CysC, HCY, IS, 24 h urinary protein, IL-6, TGF-β1, α-SMA, TGF-β1, p-p38 MAPK protein expressions and renal fibrosis degree(P<0.05, P<0.01). CONCLUSIONDischarging Fu-organ and Removing Turbidity Method can delay renal fibrosis progression in chronic kidney disease rats by reducing uremic toxins and inhibiting activated TGF-β1/p38 MAPK signaling pathway.
AIM To investigate the regulatory effects of Discharging Fu-organ and Removing Turbidity Method on TGF-β1/p38 MAPK signaling pathway in chronic kidney disease rats.METHODS Thirty rats were randomly divided into blank group, model group, Discharging Fu-organ and Removing Turbidity Method group and Dahuang Formula Granules group. The rat model for chronic kidney disease was established by intragastric administration of 2.5% adenine suspension(200 mg/kg). After 8-week administration, renal function indices, renal pathological changes, 24 h urinary protein, uremic toxins, TGF-β1/p38 MAPK signaling pathway and renal fibrosis degree were detected.RESULTS Compared with the model group, the Discharging Fu-organ and Removing Turbidity Method group demonstrated significantly decreased BUN, Scr, CysC, HCY, IS, 24 h urinary protein, IL-6, TGF-β1, α-SMA, TGF-β1, p-p38 MAPK protein expressions and renal fibrosis degree(P<0.05, P<0.01). CONCLUSIONDischarging Fu-organ and Removing Turbidity Method can delay renal fibrosis progression in chronic kidney disease rats by reducing uremic toxins and inhibiting activated TGF-β1/p38 MAPK signaling pathway.
引文
[1] 戴铭卉,孔薇.泄浊排毒方对慢性肾脏病大鼠模型蛋白结合型尿毒症毒素清除的影响[J].中国中医急症,2017,26(7):1160-1162,1171.
[2] Tu Y,Sun W,Wan Y G,et al.Huangkui capsule,an extract from Abelmoschus manihot (L.) medic,ameliorates adriamycin-induced renal inflammation and glomerular injury via inhibiting p38MAPK signaling pathway activity in rats[J].J Ethnopharmacol,2013,147(2):311-320.
[3] Hong F,Wu N,Ge Y,et al.Nanosized titanium dioxide resulted in the activation of TGF-β/Smads/p38MAPK pathway in renal inflammation and fibration of mice[J].J Biomed Mater Res A,2016,104(6):1452-1461.
[4] 霍振霞,王保兴.p38MAPK在氧化应激诱导肾间质纤维化中的研究进展[J].中华临床医师杂志(电子版),2016,10(7):1029-1032.
[5] Chin B Y,Mohsenin A,Li S X,et al.Stimulation of pro-α1 (Ⅰ) colagen by TGF-β1 in mesangial cells:role of the p38MAPK pathway[J].Am J Physiol Renal Physiol,2001,280(3):F495-F504.
[6] 赵亚亚,钟成,李悦,等.TGF-β1介导的Smad通路在肾脏纤维化中的作用及机制[J].解放军预防医学杂志,2018,36(4):427-430,458.
[7] Desmoulière A,Geinoz A,Gabbiani F,et al.Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts[J].J Cell Biol,1993,122(1):103-111.
[8] Gruden G,Zonca S,Hayward A,et al.Mechanical stretch-induced fibronectin and transforming growth factor-β1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent[J].Diabetes,2000,49(4):655-661.
[9] Xi P P,Xu Y Y,Chen X L,et al.Role of the prostaglandin E2 receptor agonists in TGF-β1-induced messangial cell damage[J].Biosci Rep,2016,36(5):e00383.
[10] 张良,杨召聪,顾亚琴,等.马兜铃酸Ⅰ激活大鼠肾脏p38 MAPK通路并导致肾细胞凋亡的研究[J].中药新药与临床药理,2015,26(5):576-581.
[11] 何东元,王笑云,王宁宁,等.大黄酸抑制肾间质成纤维细胞激活的实验研究[J].中华肾脏病杂志,2006,22(2):105-108.
[12] 秦建华,陈明,陈廷芳.p38丝裂原活化蛋白激酶在大鼠肾小管上皮细胞转分化中的作用及大黄素的干预研究[J].现代中西医结合杂志,2009,18(10):1095-1097.
[13] 余彦霖,肖堂利,刘亮,等.硫酸吲哚酚促进肾纤维化的机制研究[J].第三军医大学学报,2016,38(2):119-123.
[2] Tu Y,Sun W,Wan Y G,et al.Huangkui capsule,an extract from Abelmoschus manihot (L.) medic,ameliorates adriamycin-induced renal inflammation and glomerular injury via inhibiting p38MAPK signaling pathway activity in rats[J].J Ethnopharmacol,2013,147(2):311-320.
[3] Hong F,Wu N,Ge Y,et al.Nanosized titanium dioxide resulted in the activation of TGF-β/Smads/p38MAPK pathway in renal inflammation and fibration of mice[J].J Biomed Mater Res A,2016,104(6):1452-1461.
[4] 霍振霞,王保兴.p38MAPK在氧化应激诱导肾间质纤维化中的研究进展[J].中华临床医师杂志(电子版),2016,10(7):1029-1032.
[5] Chin B Y,Mohsenin A,Li S X,et al.Stimulation of pro-α1 (Ⅰ) colagen by TGF-β1 in mesangial cells:role of the p38MAPK pathway[J].Am J Physiol Renal Physiol,2001,280(3):F495-F504.
[6] 赵亚亚,钟成,李悦,等.TGF-β1介导的Smad通路在肾脏纤维化中的作用及机制[J].解放军预防医学杂志,2018,36(4):427-430,458.
[7] Desmoulière A,Geinoz A,Gabbiani F,et al.Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts[J].J Cell Biol,1993,122(1):103-111.
[8] Gruden G,Zonca S,Hayward A,et al.Mechanical stretch-induced fibronectin and transforming growth factor-β1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent[J].Diabetes,2000,49(4):655-661.
[9] Xi P P,Xu Y Y,Chen X L,et al.Role of the prostaglandin E2 receptor agonists in TGF-β1-induced messangial cell damage[J].Biosci Rep,2016,36(5):e00383.
[10] 张良,杨召聪,顾亚琴,等.马兜铃酸Ⅰ激活大鼠肾脏p38 MAPK通路并导致肾细胞凋亡的研究[J].中药新药与临床药理,2015,26(5):576-581.
[11] 何东元,王笑云,王宁宁,等.大黄酸抑制肾间质成纤维细胞激活的实验研究[J].中华肾脏病杂志,2006,22(2):105-108.
[12] 秦建华,陈明,陈廷芳.p38丝裂原活化蛋白激酶在大鼠肾小管上皮细胞转分化中的作用及大黄素的干预研究[J].现代中西医结合杂志,2009,18(10):1095-1097.
[13] 余彦霖,肖堂利,刘亮,等.硫酸吲哚酚促进肾纤维化的机制研究[J].第三军医大学学报,2016,38(2):119-123.