Khaksari Mohammad, Rajizadeh Mohammad Amin, Bejeshk Mohammad Abbas, Soltani Zahra, Motamedi Sina, Moramdi Fatemeh, Islami Masoud, Shafa Shahriyar, Khosravi Sepehr
Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Iran J Basic Med Sci. 2018 Jun;21(6):615-620. doi: 10.22038/IJBMS.2018.26586.6512.
Neuroprotection is created following the inhibition of angiotensin II type 1 receptor (AT1R). Therefore, the purpose of this research was examining AT1R blockage by candesartan in diffuse traumatic brain injury (TBI).
Male rats were assigned into sham, TBI, vehicle, and candesartan groups. Candesartan (0.3 mg/kg) or vehicle was administered IP, 30 min post-TBI. Brain water and Evans blue contents were determined, 24 and 5 hr after TBI, respectively. Intracranial pressure (ICP) and neurologic outcome were evaluated at -1, 1, 4 and 24 hr after TBI. Oxidant index [malondialdehyde (MDA)] was determined 24 hr after TBI.
Brain water and Evans blue contents, and MDA and ICP levels increased in TBI and vehicle groups in comparison with the sham group. Candesartan attenuated the TBI-induced brain water and Evans blue contents, and ICP and MDA enhancement. The neurologic score enhanced following candesartan administration, 24 hr after TBI.
The blockage of AT1R may be neuroprotective by decreasing ICP associated with the reduction of lipid peroxidation, brain edema, and blood-brain barrier (BBB) permeability, which led to the improvement of neurologic outcome.
抑制1型血管紧张素II受体（AT1R）可产生神经保护作用。因此，本研究的目的是检测坎地沙坦对弥漫性创伤性脑损伤（TBI）中AT1R的阻断作用。
将雄性大鼠分为假手术组、TBI组、溶剂对照组和坎地沙坦组。在TBI后30分钟腹腔注射坎地沙坦（0.3mg/kg）或溶剂。分别在TBI后24小时和5小时测定脑含水量和伊文思蓝含量。在TBI后-1、1、4和24小时评估颅内压（ICP）和神经功能结局。在TBI后24小时测定氧化指数[丙二醛（MDA）]。
与假手术组相比，TBI组和溶剂对照组的脑含水量、伊文思蓝含量、MDA和ICP水平升高。坎地沙坦减轻了TBI诱导的脑含水量、伊文思蓝含量以及ICP和MDA的升高。在TBI后24小时给予坎地沙坦后神经评分提高。
阻断AT1R可能具有神经保护作用，其机制可能是通过降低ICP，同时减少脂质过氧化、脑水肿和血脑屏障（BBB）通透性，从而改善神经功能结局。
