Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats

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Abstract

Objective: To investigate the effects and mechanisms of dexmedetomidine (Dex) on model rats of diabetic nephropathy (DN). Methods: Rats were divided into NC, model, Dex-L (1μg/ kg), Dex-M (5μg/kg) and Dex-H (10μg/kg) groups. Rats in all groups except in the NC group were injected with streptozotocin (STZ) combined with right nephrectomy. Rats in Dex (1, 5 and 10μg/kg) groups received gavage with Dex (1, 5 and 10μg/kg). After 4 weeks, rats were sacrificed and kidneys were collected. HE staining was performed for a renal injury. Masson staining was applied to detect the fibrotic accumulation in rat kidney. Radioimmunoassay was used to test the renal function. Immunohistochemical method was used to detect protein expressions of RhoA, p-MYPT and Nox4 in rat kidney. Results: Compared with the NC group, the levels of urine microalbumin in protein, α1-MG and β2-MG, renal fibrotic accumulation, RhoA, p-MYPT, Nox4 and α-SMA in model group increased significantly (P<0.001, respectively). Compared with the model group, Dex low, medium and high groups improved the deposition of renal fiber in rats, inhibited the expression levels of microalbumin, α1-MG and β2-MG in urine and decreased expression of RhoA, p-MYPT, Nox4 and α-SMA proteins (P<0.05, P<0.01). Conclusion: Dex is possible to inhibit the expression of α-SMA and renal fibrous substance deposition in rat kidney via RhoA/ROCK/Nox4 signaling pathway, thereby reducing early kidney damage in model rats.

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Jihua, C., Cai, C., Xubin, B., & Yue, Y. (2020). Effects of dexmedetomidine on the RhoA /ROCK/ Nox4 signaling pathway in renal fibrosis of diabetic rats. Open Medicine (Poland), 14(1), 890–898. https://doi.org/10.1515/med-2019-0105

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