NEUROPROTECTIVE AND ANTI-INFLAMMATORY ACTIVITIES OF ATORVASTATIN IN A RAT CHRONIC CONSTRICTION INJURY MODEL

被引：37

作者：

Chu, L. W. ^{[6
]}

Chen, J. Y. ^{[4
,5
]}

Yu, K. L. ^{[3
]}

Cheng, K. I. ^{[2
]}

Chen, I. J. ^{[1
]}

Wu, P. C. ^{[6
]}

Wu, B. N. ^{[1
]}

机构：

[1] Kaohsiung Med Univ, Coll Med, Sch Med, Dept Pharmacol, Kaohsiung 807, Taiwan

[2] Kaohsiung Med Univ & Hosp, Coll Med, Sch Med, Dept Anesthesiol, Kaohsiung, Taiwan

[3] Pingtung Christian Hosp, Div Anesthesiol, Pingtung, Taiwan

[4] Natl Sun Yat Sen Univ, Inst Biol Sci, Kaohsiung 80424, Taiwan

[5] Kaohsiung Vet Gen Hosp, Dept Neurosurg, Kaohsiung, Taiwan

[6] Kaohsiung Med Univ, Coll Pharm, Sch Pharm, Kaohsiung 807, Taiwan

来源：

INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY | 2012年 / 25卷 / 01期

关键词：

Atorvastatin; chronic constriction injury; neuropathic pain; neuroprotection; neuroinflammation; ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; INDUCED NEUROPATHIC PAIN; NF-KAPPA-B; PHOSPHATIDYLINOSITOL; 3-KINASE; NERVOUS-SYSTEM; UP-REGULATION; SPINAL-CORD; NEUROGENESIS; ANGIOGENESIS;

D O I：

10.1177/039463201202500124

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Atorvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including sham-operated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3, 7, 14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity by inhibition of TGF-beta, pI kappa B/I kappa B, NF kappa B, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAkt/Akt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.

引用

页码：219 / 230

页数：12

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