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替米沙坦在脊髓损伤治疗中的研发:大鼠的临床前研究

Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats.

作者信息

Lin Chien-Min, Tsai Jo-Ting, Chang Chen Kuei, Cheng Juei-Tang, Lin Jia-Wei

机构信息

Department of Neurosurgery, Shuang Ho Hospital-Taipei Medical University, Tainan City, Taiwan.

Department of Radiation Oncology, Shuang Ho Hospital-Taipei Medical University, Tainan City, Taiwan.

出版信息

Drug Des Devel Ther. 2015 Aug 14;9:4709-17. doi: 10.2147/DDDT.S86616. eCollection 2015.

Abstract

BACKGROUND

Decrease of peroxisome proliferator-activated receptors-δ (PPARδ) expression has been observed after spinal cord injury (SCI). Increase of PPARδ may improve the damage in SCI. Telmisartan, the antihypertensive agent, has been mentioned to increase the expression of PPARδ. Thus, we are going to screen the effectiveness of telmisartan in SCI for the development of it in clinical application.

METHODS

In the present study, we used compressive SCI in rats. Telmisartan was then used to evaluate the influence in rats after SCI. Change in PPARδ expression was identified by Western blots. Also, behavioral tests were performed to check the recovery of damage.

RESULTS

Recovery of damage from SCI was observed in telmisartan-treated rats. Additionally, this action of telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARδ. However, metformin at the dose enough to activate adenosine monophosphate-activated protein kinase failed to produce similar action as telmisartan. Thus, mediation of adenosine monophosphate-activated protein kinase in this action of telmisartan can be rule out. Moreover, telmisartan reversed the expressions of PPARδ in rats with SCI.

CONCLUSION

The obtained data suggest that telmisartan can improve the damage of SCI in rats through an increase in PPARδ expression. Thus, telmisartan is useful to be developed as an agent in the therapy of SCI.

摘要

背景

脊髓损伤(SCI)后已观察到过氧化物酶体增殖物激活受体δ(PPARδ)表达降低。PPARδ表达增加可能改善SCI损伤。已提到抗高血压药物替米沙坦可增加PPARδ的表达。因此,我们将筛选替米沙坦在SCI中的有效性,以便将其开发用于临床应用。

方法

在本研究中,我们对大鼠进行了压迫性SCI。然后使用替米沙坦评估其对SCI后大鼠的影响。通过蛋白质免疫印迹法鉴定PPARδ表达的变化。此外,进行行为测试以检查损伤的恢复情况。

结果

在替米沙坦治疗的大鼠中观察到SCI损伤的恢复。此外,替米沙坦的这种作用在足以阻断PPARδ的剂量下被GSK0660抑制。然而,足以激活单磷酸腺苷激活蛋白激酶的剂量的二甲双胍未能产生与替米沙坦类似的作用。因此,可以排除单磷酸腺苷激活蛋白激酶在替米沙坦这一作用中的介导作用。此外,替米沙坦逆转了SCI大鼠中PPARδ的表达。

结论

获得的数据表明,替米沙坦可通过增加PPARδ表达来改善大鼠的SCI损伤。因此,替米沙坦作为一种治疗SCI的药物具有开发价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cdb/4544623/d178f401946a/dddt-9-4709Fig1.jpg

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