Diminazene对慢性脑低灌注大鼠脑内炎症反应影响及机制研究  

Effects and mechanism study of Diminazene on brain inflammation of chronic cerebral hypoperfusion rats

作　　者：陆俊玲 薛晓 段瑞 张颖冬[1] LU Jun-ling;XUE Xiao;DUAN Rui(Department of Neurology,Nanjing Hospital Affiliated to Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京医科大学附属南京医院(南京市第一医院)神经内科,210006 [2]中国药科大学基础医学与临床药学学院

出　　处：《临床神经病学杂志》2020年第4期300-304,共5页Journal of Clinical Neurology

基　　金：国家自然科学基金(81771140);江苏省医学创新团队:CXTDA(2017030)。

摘　　要：目的研究Diminazene(DIZE)对慢性脑低灌注(CCH)大鼠脑内炎症反应的影响及潜在机制。方法建立CCH大鼠模型,随机分为假手术组、CCH组、CCH+低剂量DIZE组(2 mg/kg)、CCH+高剂量DIZE组(10 mg/kg)。ELISA检测大鼠脑组织IL-1β、IL-12、IL-6、TNF-α、血管紧张素(Ang)-(1-7)的变化;PCR检测Mas受体(MasR)变化;通过比色试剂盒检测血管紧张素转化酶2(ACE2)活性的变化。结果与假手术组相比,CCH组脑组织IL-1β、IL-12、IL-6、TNF-α水平明显升高(均P<0.05),ACE2活性、MasR mRNA、Ang-(1-7)水平明显降低(均P<0.05)。与CCH组相比,低剂量及高剂量DIZE组ACE2活性、MasR mRNA、Ang-(1-7)水平显著升高(均P<0.05),低剂量及高剂量DIZE组炎症因子IL-6、IL-12、TNF-α水平及高剂量DIZE组IL-1β显著降低(均P<0.05)。除IL-12外,上述变化呈剂量依赖性,仅高剂量DIZE能够使炎症因子IL-1β降低(P<0.05)。结论 Diminazene可能通过激活脑内ACE2-Ang-(1-7)-MasR轴降低CCH大鼠脑内的炎症反应。Objective To study the effect of Diminazene(DIZE) on the inflammatory response in the brain of rats with chronic cerebral hypoperfusion(CCH), and to investigate the possible underlying mechanisms. Methods The CCH rat model were established, and rats were randomly divided into sham operation group, CCH group, CCH+low dose DIZE group(2 mg/kg), CCH+high dose DIZE group(10 mg/kg). The levels of IL-1β, IL-12, IL-6, TNF-α, angiotensin(Ang)-(1-7) in rat brain tissue were detected by ELISA. The expression of Mas receptor(MasR) was detected by PCR. The activity of angiotensin-converting enzyme 2(ACE2) was detected by a colorimetric kit. Results Compared with those in sham operation group, the levels of IL-1β, IL-12, IL-6 and TNF-α in the CCH group were significantly increased(all P<0.05), while ACE2 activity, MasR mRNA expression and Ang-(1-7) levels were significantly decreased(all P<0.05). Compared with those in CCH group, ACE2 activity, MasR mRNA expression and Ang-(1-7) levels in low dose DIZE group and high dose DIZE group were significantly increased(all P<0.05), while the levels of IL-6, IL-12 and TNF-α in low dose and high dose DIZE group and IL-6 level in high dose DIZE group were significantly decreased(all P<0.05). The aforementioned effects were dose-dependent, in addition to IL-12. Only high dose DIZE could decrease the IL-1β level(P<0.05). Conclusion Diminazene may reduce the neuroinflammatory response in rats with chronic cerebral hypoperfusion by activating the brain ACE2-Ang-(1-7)-MasR axis.

关 键 词：DIMINAZENE 慢性脑低灌注 血管性认知障碍 炎症 

分 类 号：R51[医药卫生—内科学]