Effects of Shenshuai Yangzhen Capsule on SOCS3 in Hapotholums in Malnutrition Rats with Chronic Renal Failure by 5/6 Nephrectomy
Abstract:ObjectiveTo investigate the effects of Shenshuai Yangzhen capsule on SOCS3 in hypothalamus in malnutrition rats with chronic renal failure by 5/6 nephrectomy. MethodsSD rats were received 5/6 nephrectomy for preparation of CRF models, and fed with 4% casein at the same time. The blood parameters, like BUN, SCr, Alb,Hb and weight in CRF rats were determined. We observed when malnutrition began. Those in condition were randomized into CRF control group, ketosteric group, Shenshuai Yangzhen group, and normal control group. After 4-week treatment as indicated, the blood leptin in CRF rats were determined by radioimmunoassay. The protein expressions of SOCS3 were assessed respectively by immunohestchemistry.ResultsCompared with those in the CRF group, the plasma blood urea nitrogen and serum creatinine concentrations and leptin contents in Shenshuai Yangzhen group were significantly lower with substantially elevated plasma album and haemoglobin. Compared with the normal group rats, the respective expression of SOCS3 significantly increased in rats with surgically induced renal failure (two-stage subetotal nephrectomy) (P<0.001). After treatment with Shenshuai Yangzhen capsule, the expression of SOCS3 in the CRF rats was upregulated (all P<0.05). ConclusionSOCS3 proteins may be involved in the malnutrition associated with CRF. Upregulation of SOCS3 may be responsible for the malnutrition effects of Shenshuai Yangzhen capsule in CRF rats.
Key words:Shenshuai Yangzhen capsule; 5/6 nephrectomy; Hapotholums; Immunohestchemistry; Signal transducer protein
动物实验表明瘦素(Leptin)在下丘脑的信号传导主要涉及JAK2/STAT3通路。OBR配体与OBRb受体结合使OBRb细胞内的酪氨酸残基磷酸化,并通过转磷酸作用活化JAK2。磷酸化的OBRb形成了一个与STAT3(信号传导转录活化因子Signal transducer and activator of transcription,STAT)单体连接的位点,STAT3一旦到达受体在C端的705位点被JAK2磷酸化,使STAT3形成同型或异型二聚体,并转移定位到细胞核,与特定基因启动子区域的DNA元件或其他的转录因子或附属的蛋白相互作用,调节靶基因的转录。Leptin在活化JAK2/STAT3信号传导途径的同时,也促进相关抑制剂的表达,包括细胞因子信号传导抑制剂(Suppressor of cytokine signaling,SOCS)。在转染了SOCS3基因的COS细胞,当Leptin存在时SOCS3可与JAK2结合,并抑制Leptin诱导的JAK2的各氨酸磷酸化,提示SOCS3通过与JAK2结合而抑制了JAK2的各氨酸激酶活性,从而抑制了OBR后的JAK/STAT信号传导通路。5/6肾切除可造成典型的慢性肾衰竭,本实验观察了肾衰养真胶囊对5/6肾切慢性肾衰竭营养不良模型大鼠下丘脑信号传导蛋白SOCS3表达的影响,从分子水平探讨肾衰养真胶囊如何通过对SOCS3蛋白的调节作用而发挥改善营养不良的作用机制。
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