Lan Lin-Fang, Zheng Lu, Yang Xian, Ji Xiao-Tan, Fan Yu-Hua, Zeng Jin-Sheng
Department of Neurology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
CNS Neurosci Ther. 2015 May;21(5):410-6. doi: 10.1111/cns.12374. Epub 2015 Jan 22.
Cerebrovascular white matter lesion (WML) is a major subtype of cerebral small vessel disease. Clinical drugs are not available for WML. We investigated whether peroxisome proliferator-activated receptor-γ agonist pioglitazone, with properties of vascular protection and antiinflammation, exerts beneficial effect in hypertensive WML rats.
Stroke-prone renovascular hypertensive rats (RHRSP) were treated with pioglitazone for 12 weeks. Morris water maze experiment was conducted to assess cognition. WML was observed by Luxol fast blue staining. Smooth muscle actin-alpha, collagen I, collagen IV, glial fibrillary acidic protein, and ionized calcium-binding adaptor molecule-1 were evaluated by immunohistochemistry. Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in brain and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were detected.
Pioglitazone significantly attenuated WML in corpus callosum, caudate putamen, external capsule, and internal capsule. Cognitive impairment in RHRSP was ameliorated by pioglitazone. Pioglitazone attenuated arteriolar remodeling and reduced sICAM-1 level in serum. Pioglitazone decreased the proliferation of microglia and astrocyte and lowered the expression of proinflammatory cytokines IL-1β and TNF-α in the white matter.
Long-term treatment of pioglitazone has beneficial effect on hypertension-induced WML and cognition decline, which may partly through its effect on attenuation of arteriolar remodeling, endothelial activation, and brain inflammation.
脑血管白质病变（WML）是脑小血管病的一种主要亚型。目前尚无针对WML的临床可用药物。我们研究了具有血管保护和抗炎特性的过氧化物酶体增殖物激活受体γ激动剂吡格列酮是否对高血压性WML大鼠产生有益作用。
对易卒中型肾血管性高血压大鼠（RHRSP）给予吡格列酮治疗12周。进行莫里斯水迷宫实验以评估认知功能。通过Luxol固蓝染色观察WML。采用免疫组织化学法评估平滑肌肌动蛋白α、I型胶原、IV型胶原、胶质纤维酸性蛋白和离子钙结合衔接分子1。检测脑内白细胞介素-1β（IL-1β）和肿瘤坏死因子α（TNF-α）以及血清中可溶性细胞间黏附分子-1（sICAM-1）。
吡格列酮显著减轻了胼胝体、尾状核、外囊和内囊的WML。吡格列酮改善了RHRSP的认知障碍。吡格列酮减轻了小动脉重塑并降低了血清中sICAM-1水平。吡格列酮减少了小胶质细胞和星形胶质细胞的增殖，并降低了白质中促炎细胞因子IL-1β和TNF-α的表达。
长期使用吡格列酮对高血压诱导的WML和认知功能下降具有有益作用，这可能部分是通过其对减轻小动脉重塑、内皮激活和脑炎症的作用实现的。
