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氯沙坦可预防神经原性瘫痪膀胱大鼠的膀胱纤维化并保护肾功能。

Losartan prevents bladder fibrosis and protects renal function in rat with neurogenic paralysis bladder.

机构信息

Pediatric Urodynamic Centre, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Henan Joint International Pediatric Urodynamic Laboratory, Zhengzhou, China.

出版信息

Neurourol Urodyn. 2021 Jan;40(1):137-146. doi: 10.1002/nau.24567.

Abstract

AIMS

To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB).

MATERIALS AND METHODS

Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (P ) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (P ) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin Ⅱ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor β1 (TGFβ1), Collagen Ⅲ, and collagen fibrin in the bladder tissue were detected too.

RESULTS

ΔC in TSNG and LSTG decreased significantly compared to the CG. P in TSNG and LSTG were significantly higher than P in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang Ⅱ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFβ1, Collagen Ⅲ, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG.

CONCLUSION

Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFβ1 and consequently may reduce kidney damage from occurring.

摘要

目的

研究氯沙坦对神经原性膀胱麻痹(NPB)大鼠膀胱纤维化的预防作用及对肾功能的保护作用。

材料与方法

将大鼠分为横断脊髓神经组(TSNG)、横断脊髓神经+氯沙坦组(LSTG)和对照组(CG)。术后第 32 天,通过膀胱测压法测量各组大鼠的膀胱容量(BC)、膀胱顺应性(ΔC)和膀胱漏尿压(P )。检测各组大鼠的肾功能和血液中血管紧张素Ⅱ(Ang II)的表达量,并检测膀胱组织中 Ang II、血管紧张素Ⅱ 1 型受体(AT1)、转化生长因子 β1(TGFβ1)、Ⅲ型胶原和胶原纤维的表达量。

结果

与 CG 相比,TSNG 和 LSTG 的 ΔC 明显降低,P 明显升高。与 CG 相比,TSNG 和 LSTG 的肾功能明显下降,但 LSTG 的肾功能优于 TSNG。与 CG 相比,TSNG 和 LSTG 血液和膀胱组织中的 Ang Ⅱ明显增加。AT1 在所有大鼠的膀胱组织中均有表达。与 CG 和 LSTG 相比,TSNG 中 TGFβ1、Ⅲ型胶原和胶原纤维的表达水平明显升高,而 CG 和 LSTG 之间差异无统计学意义。

结论

氯沙坦可能通过阻断 Ang II/AT1/TGFβ1 信号的上调来预防 NPB 纤维化,从而减少肾损伤的发生。

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