清热化湿祛瘀法对慢性肾衰竭湿热证患者瘦素介导的JAK/STAT信号通路的影响

Influence of heat-clearing dampness-resolving stasis-dispelling therapy on JAK/STAT signaling pathway mediated by Leptin in patients with chronic renal failure-damp-heat pattern

目的观察清热化湿祛瘀中药清肾颗粒对慢性肾衰竭(CRF)湿热证患者血清瘦素(Leptin)、Janus激酶/信号转导与转录活化因子(JAK/STAT)信号通路中Janus激酶2(JAK2)蛋白及信号转导和转录激活因子3(STAT3)蛋白表达的影响,探讨清肾颗粒治疗CRF患者的作用机制。方法68例CRF湿热证患者,随机数字表法分为治疗组和对照组,每组34例,实际完成60例,治疗组29例,对照组31例。治疗组及对照组给予西医基础治疗,治疗组加用清肾颗粒,每日3次,每次1袋,疗程均为12周。观察2组患者临床疗效、治疗前后血肌酐(Scr)、肾小球滤过率估算值(e GFR)以及血清Leptin、JAK2蛋白、STAT3蛋白变化情况。结果治疗组临床疗效和中医证候疗效总有效率为86.21%(25/29)和82.76%(24/29),优于对照组的58.06%(18/31)和54.84%(17/31),差异有统计学意义(P<0.05)。与本组治疗前比较,治疗后治疗组Scr水平明显下降(P<0.01),e GFR水平明显升高(P<0.01),且优于对照组同期(P<0.05)。与本组治疗前比较,治疗后治疗组Leptin、JAK2、STAT3水平均明显降低(P<0.01),且均优于对照组同期(P<0.05或P<0.01)。结论清肾颗粒可降低CRF湿热证患者血清Leptin、JAK2蛋白及STAT3蛋白水平,抑制瘦素介导的JAK/STAT信号通路的活化,进而改善CRF湿热证患者临床症状和肾功能。

Objective To observe the influences of Qingshen（ Kidney-Clearing） Granules,with effects of clearing heat,resolving dampness and dispelling stasis,on expressions of Janus-activated kinase 2（ JAK2） and signal transducers and activator of transcriptions 3（ STAT3） in Janus-activated kinasesignaltransducer and activator of transcription（ JAK/STAT） signaling pathway mediated by Leptin in patients with chronic renal failure（ CRF）-damp-heat pattern,and investigate the mechanism of Qingshen Granules in treatment of CRF. Methods The patients with CRF-damp-heat pattern（ n = 68） were randomly divided into treatment group and control group（ each n = 34）. The study was completed actually in 60 patients,and 29 in treatment group and 31 in control group. All 2 groups were given basic treatment of Western medicine,and treatment group was additionally given Qingshen Granules（ thrice daily and 1 bas every time） for 12 weeks. The clinical efficacy and changes of serum creatinine（ SCr）,estimated glomerular filtration rate（ e GFR）,serum Leptin,JAK2 and STAT3 were observed in 2 groups.Results The clinical efficacy was 86. 21%（ 25/29） and total effective rate of TCM patterns was82. 76%（ 24/29） in treatment group,and 58. 06%（ 18/31） and 54. 84%（ 17/31） in control group（ P〈0. 05）. After treatment,the level of SCr decreased significantly（ P〈0. 01） and level of GFR increased significantly（ P〈0. 01） in treatment group compared with those before treatment,which were superior to those in control group at the same term（ P〈0. 05）. After treatment,the level of Leptin,and expressions of JAK2 and STAT3 decreased significantly（ P〈0. 01） in treatment group compared with those before treatment,which were superior to those in control group at the same term（ P〈0. 05 or P〈0. 01）. Conclusion Qingshen Granules can reduce the level of Leptin and expressions of JAK2 and STAT3,inhibit the activation of JAK/STAT signaling pathway mediated by Leptin,relieve clinical symptoms and improve kidney function in patients with CRF-damp-heat pattern.