卡格列净对肾病综合征的治疗作用及超声评价

Therapeutic Effect of Canagliflozin on Nephrotic Syndrome and Its Ultrasonic Evaluation

【目的】探讨抗糖药物卡格列净(CGLZ)对阿霉素所致肾病综合征(NS)模型大鼠的治疗作用,以及超声造影(CEUS)联合彩色多普勒血流显像(CDFI)在治疗过程中的评价作用。【方法】56只SD雄性大鼠随机分为正常组(NG)、模型组(MG)、泼尼松(PAT)组(PG)、小剂量CGLZ组(LSCG)、大剂量CGLZ组(HSCG)、小剂量CGLZ+PAT组(LUCG)和大剂量CGLZ+PAT组(HUCG),每组8只。采用阿霉素2次尾静脉注射法诱导制备NS大鼠模型,以常规PAT治疗为参照予以每日药物灌胃处理,连续6周。在灌胃前1 d和灌胃2、4、6周末分别行24h-UTP定量检测,灌胃6周末行右肾动脉CDFI及右肾CEUS检查,次日取腹主动脉血行血清学检测。【结果】与NG大鼠的检测指标相比,MG大鼠的24 h-UTP升高(P<0.01),血清ALB降低,TG、TC、LDL升高(P<0.01),CDFI显示RRCT变薄(P<0.01),肾动脉血流指标RA-PI、RA-RI、RA-S/D升高(P<0.05),CEUS图像显示TIC曲线参数TTP、AT、AUC升高,DPI、A下降(P<0.01)。药物治疗后,与MG大鼠的检测指标相比,24 h-UTP检测结果显示2周后仅LSCG组下降(P<0.01),6周后各药物组均明显下降(P<0.01);血清学检测结果显示6周后所有CGLZ治疗组大鼠的血清ALB升高(P<0.05),LSCG大鼠的TG下降(P<0.01),LUCG大鼠的TC、LDL下降(P<0.05);CDFI检查显示所有CGLZ治疗组大鼠肾脏的RRCT变薄程度减轻(P<0.01),LSCG大鼠的RA-PI、PG大鼠的RA-RI以及PG、LSCG、HSCG、LUCG大鼠的RA-S/D均降低(P<0.05);CEUS检查显示所有药物治疗组大鼠肾脏TIC曲线的TTP、AT、AUC降低(P<0.01),PG、HSCG、LUCG、HUCG大鼠的DPI升高(P<0.01)。【结论】CGLZ具有治疗NS作用,以小剂量用药为最佳。CEUS联合CDFI检查可用来评估NS模型大鼠及其药物治疗前后的肾脏形态及血流动力学变化,有助于指导临床应用。

【Objective】 To investigate the therapeutic effect of antidiabetic drug canagliflozin(CGLZ) on adriamycininduced nephrotic syndrome(NS) in rats, and the evaluation of contrast-enhanced ultrasound(CEUS) combined with color Doppler flow imaging(CDFI) during the treatment.【Methods】 A total of 56 male SD rats were randomly divided into normal group(NG), model group(MG), prednisone(PAT) group(PG), low-dose single CGLZ group(LSCG), high-dose single CGLZ group(HSCG), low-dose CGLZ + PAT group(LUCG) and high-dose CGLZ + PAT group(HUCG), with 8rats in each group. The NS model in rats was induced by injecting adriamycin twice into the tail vein, and then the NS rats were treated by intragastric administration daily for 6 weeks with reference of PAT. Twenty-four hour urine total protein(24 h-UTP) was assessed one day before the start of oral administration and at the end of 2, 4 and 6 weeks after oral administration, respectively. CDFI and CEUS were performed on the right renal artery at the end of 6 weeks after oral administration, and the blood of abdominal aorta was taken for serological test the next day.【Results】 Compared with those detection index of NG rats, the 24-hour UTP of MG rats increased(P<0.01), the serum ALB decreased and TG, TC, LDL increased(P<0.01), and CDFI shows that RRCT was thinner(P<0.01) and the renal artery blood flow indicators RA-PI, RA-RI, RA-S/D all increased(P<0.05), and CEUS image shows that the TIC curve parameters TTP, AT, AUC all increased and DPI decrease in MG rats(P<0.01). After drug treatment, compared with those detection index of MG rats, 24h-UTP decrease in LSCG after 2 weeks(P<0.01), and decrease significantly in all drug groups after 6 weeks(P<0.01);the serological test results show that the serum ALB in all CGLZ groups increased(P<0.05), TG decrease in LSCG(P<0.01), TC and LDL also decrease in LUCG after 6 weeks(P<0.05);CDFI shows that the RRCT thinning degree in all CGLZ is reduced(P<0.01), and the RA-PI in LSCG, RA-RI in PG, and RA-S/D in PG, LSCG, HSCG and LUCG rats all decreased(P<0.05);CEUS shows that the TTP, AT and AUC of renal TIC curve in drug treatment groups all decreased(P<0.01), and the DPI in PG, HSCG, LUCG and HUCG rats increased(P<0.01).【Conclusions】 CGLZ has the effect of treating NS, and the small dose is the best. CEUS combined with CDFI can be used to evaluate the renal morphology and hemodynamic changes of NS model rats before and after drug treatment, which is helpful to guide clinical application.