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卡格列净与大豆异黄酮对1型糖尿病模型大鼠骨代谢的影响比较

Canagliflozin versus soy isoflavone for bone metabolism in model rats with type 1 diabetes mellitus

    摘要
  • 摘要:
    目的 比较卡格列净(CGLZ)和大豆异黄酮(SIF)对1型糖尿病模型大鼠骨代谢的影响。
    方法 选取40只雄性SD大鼠, 随机分为对照组、模型组、SIF组、低剂量CGLZ组、高剂量CGLZ组，每组8只。模型组和治疗组均经腹腔注射链脲佐菌素进行造模。治疗组每天灌胃，持续12周。治疗过程中及结束后，检测各组大鼠体质量、进食量、饮水量、空腹血糖(FPG)、血清白蛋白(ALB)、血钙(SCa)、血磷(SP)、血肌酐(Scr)、25-羟基维生素D(25-OH-D3)、尿蛋白(Pro)、尿肌酐(Ucr)、尿蛋白与尿肌酐比值(UPCR)以及骨代谢相关指标在体全身骨密度(TBMD)、区域骨密度(RBMD)、全身骨盐量(TBSC)、全身脂肪量(TBFM)和全身肌肉量(TBMM)。RBMD检测区域包括头、上肢、大腿、躯干、肋骨、骨盆和脊柱。
    结果 造模成功12周后，模型组、SIF组、低剂量CGLZ组、高剂量CGLZ组饮水量、进食量增加，体质量下降; 低剂量CGLZ组、高剂量CGLZ组用药后体质量增加，高剂量CGLZ组较SIF组增加更显著。低剂量CGLZ组、高剂量CGLZ组治疗第4周后以及SIF组、低剂量CGLZ组、高剂量CGLZ组治疗第8、12周后大鼠FPG均下降，治疗效果为高剂量CGLZ组>低剂量CGLZ组>SIF组。治疗12周后，各治疗组大鼠的Pro、Ucr、UPCR均下降，差异有统计学意义(P < 0.01); SIF组、低剂量CGLZ组、高剂量CGLZ组ALB水平升高, Scr水平下降，差异有统计学意义(P < 0.01); 高剂量CGLZ组25-OH-D3水平降低，差异有统计学意义(P < 0.01)。治疗12周后，高剂量CGLZ组TBSC增加，而SIF组和低剂量CGLZ组均不能升高TBMD、TBSC、TBFM、TBMM; 高剂量CGLZ组大鼠大腿，低剂量CGLZ组和高剂量CGLZ组大鼠躯干、肋骨和脊柱，以及SIF组和高剂量CGLZ组大鼠骨盆均出现骨密度增加。
    结论 CGLZ和SIF均可降低链脲佐菌素诱导的1型糖尿病模型大鼠高血糖，且前者的效果更好。在改善全身骨盐量、全身骨密度以及各部位骨密度方面，高剂量CGLZ较低剂量的效果更佳，而SIF仅对骨盆的骨密度具有一定改善作用。

     

    Abstract:
    Objective To compare the effect of canagliflozin (CGLZ) and soy isoflavone (SIF) on bone metabolism in model rats with type 1 diabetes mellitus.
    Methods Forty male SD rats were randomly divided into control group, model group, SIF group, low-dose CGLZ group and high-dose CGLZ group, with 8 rats in each group. Model group and treatment groups were intraperitoneally injected with streptozotocin for modeling. The rats in treatment groups were gavaged daily for 12 weeks. During and after treatment, the body mass, food intake, water consumption, fasting blood glucose (FPG), serum albumin (ALB), serum calcium (SCa), serum phosphorus (SP), serum creatinine (Scr), serum 25 hydroxyvitamin D (25-OH-D3), urine protein (Pro), urine creatinine (Ucr), urine protein to urine creatinine ratio (UPCR) and bone metabolism related indicatorstotal bone mineral density (TBMD), regional bone mineral density (RBMD), total body salt content (TBSC), total body fat mass (TBFM) and total body muscle mass (TBMM)of rats in each group were detected. Detection sites of RBMD included head, upper limb, thigh, trunk, rib, pelvis and spine.
    Results After 12 weeks of successful modeling, the water intake and food consumption of rats in model group, SIF group, low-dose CGLZ group and high-dose CGLZ group all increased, while the body mass decreased; after medication, the body mass of rats in low-dose CGLZ group and high-dose CGLZ group increased, and increased range of body mass in high-dose CGLZ group was significantly greater than that in the SIF group. The FPG level of rats after 4 weeks of treatment in low-dose CGLZ group and high-dose CGLZ group as well as after 8 and 12 weeks of treatment in the SIF group, low-dose CGLZ group and high-dose CGLZ group decreased, and efficacy ranking from high to low was high-dose CGLZ group, low-dose CGLZ group and SIF group. After 12 weeks of treatment, Pro, Ucr and UPCR of rats in each treatment group decreased significantly (P < 0.01); in the SIF group, low-dose CGLZ group and high-dose CGLZ group, serum ALB level increased significantly while Scr level decreased significantly(P < 0.01); the level of 25-OH-D3 in high-dose CGLZ group decreased significantly (P < 0.01). After treatment of 12 weeks, TBSC in high-dose CGLZ group increased, but TBMD, TBSC, TBFM and TBMM did not increase in SIF group and low-dose CGLZ group; the increase of bone mineral density was observed in the thigh of high-dose CGLZ group, the trunk, ribs and spine of low-dose CGLZ group and high-dose CGLZ group, and the pelvis of SIF group and high-dose CGLZ group.
    Conclusion Both CGLZ and SIF can reduce hyperglycemia induced by streptozotocin in model rats with type 1 diabetes mellitus, and the effect of the former is better. In terms of improving the total body bone salts, total body bone mineral density and bone mineral density at all sites, the effect of high-dose CGLZ is better than that of low-dose CGLZ, while SIF can only improve the bone mineral density of pelvis to a certain extent.

     

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