虫草益肾方对单侧输尿管梗阻大鼠Notch信号通路的影响
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摘要
目的:探讨虫草益肾方对(unilateral ureteral occlusion,UUO)模型大鼠Notch信号通路的调控作用。方法:80只SPF级雄性SD大鼠随机分假手术组10只及造模组30只,造模组采用UUO法进行模型制备,术后随机分为模型组、虫草益肾方组(虫草组)与厄贝沙坦组,每组20只。分别给予虫草益肾方水煎液、厄贝沙坦水溶液及蒸馏水进行灌胃,于第7天及14天收集血清及肾组织。HE染色观察其病理改变,采用Elisa法检测血清Notch1、Jagged1、Hes1蛋白的表达。结果:虫草益肾方可改善UUO大鼠肾脏的病理变化程度;模型组大鼠7天、14天血清中Notch1、Jagged1、Hes1蛋白表达与假手术组相比明显增加(P<0.05),虫草组、厄贝沙坦组大鼠7天、14天血清中Notch1、Jagged1、Hes1蛋白表达与模型组相比均减少(P<0.05)结论:虫草益肾方可改善因输尿管梗阻所致的肾脏结构病理变化,其作用可能与下调Notch1、Jagged1、Hes1蛋白表达,从而抑制Notch信号通路有关。
Objective:To investigate the effect of Chongcao Yishen Decoction on Notch signaling pathway in unilateral ureteral occlusion(UUO) model rats.Methods:80 SD rats were randomly divided into 10 sham-operated groups and 30 model-building groups.The model group was prepared by UUO method, and randomly divided into model group, Chongcao Yishen Decoction group(Chongcao group) and Irbesartan group, with 20 rats in each group.The rats were given intragastric administration of Chongcao Yishen Decoction, Irbesartan Aqueous Solution and distilled water, and serum and kidney tissue were collected on the 7 th and 14 th day.HE staining was used to observe the pathological changes of the kidney.The expression of Notch1, Jagged1 and Hes1 protein in serum was detected by Elisa method.Results:Chongcao Yishen Decoction can improve the degree of renal pathological changes in UUO rats.The expression of Notch1, Jagged1 and Hes1 in the serum of the model group rats at 7 and 14 days was significantly increased compared with the sham group(P<0.05).The protein expression of Notch1, Jagged1, and Hes1 in rats of the Chongcao group and the Irbesartan group at 7 and 14 days were decreased compared with the model group(P<0.05).Conclusion:Chongcao Yishen Decoction can improve the pathological changes of renal structure caused by ureteral obstruction, and its effect may be related to the down-regulation of Notch1, Jagged1, Hes1 protein expression, thereby inhibiting Notch signaling pathway.
Objective:To investigate the effect of Chongcao Yishen Decoction on Notch signaling pathway in unilateral ureteral occlusion(UUO) model rats.Methods:80 SD rats were randomly divided into 10 sham-operated groups and 30 model-building groups.The model group was prepared by UUO method, and randomly divided into model group, Chongcao Yishen Decoction group(Chongcao group) and Irbesartan group, with 20 rats in each group.The rats were given intragastric administration of Chongcao Yishen Decoction, Irbesartan Aqueous Solution and distilled water, and serum and kidney tissue were collected on the 7 th and 14 th day.HE staining was used to observe the pathological changes of the kidney.The expression of Notch1, Jagged1 and Hes1 protein in serum was detected by Elisa method.Results:Chongcao Yishen Decoction can improve the degree of renal pathological changes in UUO rats.The expression of Notch1, Jagged1 and Hes1 in the serum of the model group rats at 7 and 14 days was significantly increased compared with the sham group(P<0.05).The protein expression of Notch1, Jagged1, and Hes1 in rats of the Chongcao group and the Irbesartan group at 7 and 14 days were decreased compared with the model group(P<0.05).Conclusion:Chongcao Yishen Decoction can improve the pathological changes of renal structure caused by ureteral obstruction, and its effect may be related to the down-regulation of Notch1, Jagged1, Hes1 protein expression, thereby inhibiting Notch signaling pathway.
引文
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[2] 朱可可,杨波.肾间质纤维化发病机制研究进展[J].广东医学,2015,36(02):324～326
[3] Kopan R,Ilagan M X G.The Canonical Notch Signaling Pathway:Unfolding the Activation Mechanism[J].Cell,2009,137(2):216～233
[4] Cheng H T,Kopan R.The role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidney[J].Kidney International,2005,68(5):1951～1952
[5] Boor P,Ostendorf T,Floege J.Renal fibrosis:novel insights into mechanisms and therapeutic targets[J].Nature Reviews Nephrology,2010,6(11):643
[6] 陈凤,LU Zhiwei,戴恩来.中西医对肾纤维化发病机制的研究进展[J].辽宁中医杂志,2016,43(06):1243～1246
[7] 王新荣,万廷信,赵著华,等.IgA肾病中医湿热证微观辨证病理指标研究[J].中国中医药信息杂志,2015,22(08):31～35
[8] Chen L,Al-Awqati Q.Segmental expression of Notch and Hairy genes in nephrogenesis.[J].American Journal of Physiology Renal Physiology,2005,288(5):F939～52
[9] Klüppel M,Wrana J L.Turning it up a Notch:cross-talk between TGFβ and Notch signaling[J].Bioessays News & Reviews in Molecular Cellular & Developmental Biology,2005,27(2):115–118
[10] 刘琳丰,陈明,金立新,等.Notch1在TGF-β______1诱导的人肾小管上皮细胞转分化中的表达和意义[J].细胞与分子免疫学杂志,2011,27(10):1068～1071
[11] Sultana,Afroz D,Bell,et al.Eliciting the T cell fate with Notch.[C]// Seminars in Immunology,2010:254～260
[12] 姜亚丽.Notch信号调控巨噬细胞参与肾纤维化的作用及机制研究[D].第四军医大学,2015