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大豆苷元通过抑制NOX-4和RAC-1减轻链脲佐菌素诱导的糖尿病大鼠膀胱功能障碍。

Daidzein attenuates urinary bladder dysfunction in streptozotocin-induced diabetes in rats by NOX-4 and RAC-1 inhibition.

作者信息

Laddha Ankit P, Kulkarni Yogesh A

机构信息

Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, V.L. Mehta Road, Vile Parle (West), Mumbai, 400056, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2022 Aug;395(8):975-986. doi: 10.1007/s00210-022-02246-y. Epub 2022 May 11.

Abstract

Reactive oxygen species via NADPH oxidase (NOX) activation are involved in the pathogenesis of many disease conditions such as diabetes and its complications. In the present study, we have examined the effect of daidzein in the management of diabetic cystopathy. Diabetes was induced in male Sprague Dawley rats via intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg. After 6 weeks of diabetes induction, animals were treated with daidzein orally at a dose of 25, 50, and 100 mg/kg for 4 weeks. Diabetic animals showed increase (p < 0.001) in bladder capacity (4.32 ± 0.43 mL) and residual volume (2.53 ± 0.19 mL) when compared with normal control animals (2.10 ± 0.40 mL and 0.51 ± 0.12 mL res). Treatment with daidzein at dose of 50 and 100 mg/kg significantly reduced the elevated bladder capacity (2.91 ± 0.11 mL, p < 0.01 and 2.65 ± 1.13 mL, p < 0.001) and residual volume (1.40 ± 0.15 mL, p < 0.001 and 1.15 ± 0.05 mL, p < 0.001). Daidzein-treated animals also showed improvement in voiding efficiency. Elevated threshold and baseline pressure were also found to be reduced in diabetic animals after 4 weeks of daidzein treatment. Daidzein treatment also prevented the loss of antioxidant enzymes in the urinary bladder and also reduced the expression of NOX-4 and RAC-1 in the bladder. From the results, it can be concluded that daidzein showed a beneficial effect on urinary bladder dysfunction in diabetic animals.

摘要

通过烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)激活产生的活性氧参与了许多疾病状态的发病机制,如糖尿病及其并发症。在本研究中,我们研究了大豆苷元对糖尿病膀胱病的治疗作用。通过腹腔注射剂量为55mg/kg的链脲佐菌素(STZ)诱导雄性Sprague Dawley大鼠患糖尿病。糖尿病诱导6周后,动物分别以25、50和100mg/kg的剂量口服大豆苷元,持续4周。与正常对照动物(膀胱容量2.10±0.40mL,残余尿量0.51±0.12mL)相比,糖尿病动物的膀胱容量(4.32±0.43mL)和残余尿量(2.53±0.19mL)增加(p<0.001)。以50和100mg/kg剂量的大豆苷元治疗可显著降低升高的膀胱容量(2.91±0.11mL,p<0.01和2.65±1.13mL,p<0.001)和残余尿量(1.40±0.15mL,p<0.001和1.15±0.05mL,p<0.001)。大豆苷元治疗的动物排尿效率也有所改善。大豆苷元治疗4周后,糖尿病动物升高的阈值和基线压力也有所降低。大豆苷元治疗还可防止膀胱中抗氧化酶的损失,并降低膀胱中NOX-4和RAC-1的表达。从结果可以得出结论,大豆苷元对糖尿病动物的膀胱功能障碍具有有益作用。

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