补肾化痰祛瘀法联合运动体疗治疗超重/肥胖型多囊卵巢综合征的临床研究

Study on mechanism of Huangxue Yishen Formula improving chronic renal failure based on serum metabolomics

目的:观察补肾化痰祛瘀法联合运动体疗治疗超重/肥胖型多囊卵巢综合征(PCOS)的临床疗效。方法:纳入超重/肥胖型PCOS患者72例,随机分为治疗组和对照组,每组各36例。治疗组患者予补肾化痰祛瘀方联合运动治疗,对照组患者予补肾化痰祛瘀方治疗,两组疗程均为3个月。比较两组患者的临床疗效;干预前后,评估并比较两组患者的月经情况评分、Ferriman-Gallwey多毛评分、痤疮pillsbuny分级法评分、黑棘皮评分及焦虑自评量表(SAS)评分;干预前后,检测所有患者的性激素[包括促黄体生成素(LH)、卵泡刺激素(FSH)、睾酮(T)、抗缪勒激素(AMH)、LH/FSH比值]水平、糖脂代谢指标[包括空腹血糖(FPG)、空腹胰岛素(FINS)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、胰岛素抵抗指数(HOMA-IR)]水平及血清瘦素水平;干预前后,超声检测两组患者的卵巢面积。结果:(1)干预后,治疗组的临床总有效率为83.34%,对照组为50.00%,治疗组的疗效优于对照组(P<0.05)。(2)干预后,两组患者的月经情况、多毛、痤疮评分及SAS评分较干预前均明显下降(P<0.05,P<0.01),且治疗组患者的月经情况、多毛评分及SAS评分明显低于对照组(P<0.05)。(3)干预后,两组患者的LH、T、AMH水平及LH/FSH比值较干预前均降低(P<0.05,P<0.01),但两组患者的各项性激素水平组间比较差异无统计学意义(P>0.05)。(4)干预后,两组患者的FINS、HOMA-IR水平较干预前均明显降低(P<0.01),但各项糖代谢指标水平组间比较差异无统计学意义(P>0.05)。(5)干预后,治疗组患者的TG、TC、LDL-C水平明显降低(P<0.05,P<0.01),HDL-C水平升高(P<0.05),对照组患者的TC、LDL-C水平亦明显降低(P<0.05),且治疗组患者的HDL-C水平高于对照组(P<0.01)。(6)干预后,两组患者的血清瘦素水平较干预前均明显降低(P<0.01),且治疗组患者的血清瘦素水平明显低于对照组(P<0.01)。(7)干预前后,两组患者的卵巢面积组间及组内比较,差异均无统计学意义(P>0.05)。结论:补肾化痰祛瘀法联合运动体疗可有效改善超重/肥胖型PCOS患者的相关症状及体征,降低体质量,纠正糖脂代谢紊乱,减轻瘦素抵抗,提高临床疗效。

Objective:To evaluate the efficacy of Huangxue Yishen Formula in treating rats with chronic renal failure,and preliminarily reveal its metabolic regulatory mechanism through metabolomics.Methods:SD rats were divided into normal group,model group,positive drug(valsartan)group,Huangxue Yishen Formula low-dose group and high-dose groups.Chronic renal failure rat model was induced by the combination of Adriamycin(ADR)and adenine,the normal group and model group were administered with 0.9%NaCl solution daily,and the drug-treated groups were intragastrically administered with valsartan 8.33 mg/kg/d and Huangxue Yishen Formula 12.5 and 25 g/kg/d respectively for 6 consecutive weeks.During the experiment,general condition of rats was monitored,24h urine protein and renal function indexes were detected and hematoxylin-eosin(H-E)staining was performed to observe the renal pathological changes.Serum metabolic changes were analyzed by Ultra Performance Liquid Chromatography-Linear Ion Trap Quadrupole-Orbitrap-Mass Spectrometer/Mass Spectrometer(UPLC-LTQ-Orbitrap-MS/MS)to investigate the metabolic regulation mechanism of Huangxue Yishen Formula improving chronic renal failure in rats.Results:Compared with the normal group,signs of exhaustion such as body mass loss,mental depression and weakness were appeared in the rats of the model group,and 24h urine protein was significantly increased,serum creatinine(Scr)and blood urea nitrogen(BUN)were significantly increased(P<0.01),while serum albumin(Alb)was significantly decreased(P<0.01).After drug intervention,all indicators were improved to varying degrees(P<0.05,P<0.01).The pathological results showed that renal tubular injury,interstitial fibrosis and glomerular atrophy and sclerosis in the rats of the model group were effectively improved by Huangxue Yishen Formula.44 differential metabolites were identified by metabolomic study,mainly enriched in the metabolic pathways of arginine biosynthesis,glycerophospholipid metabolism,arachidonic acid metabolism and sphingolipid metabolism.Conclusion:Huangxue Yishen Formula can significantly reduce the phenomenon of urinary protein in rats with chronic renal failure,and alleviate renal impairment,and the main effect mechanism involves its regulatory effects on lipid metabolism and inflammatory damage.