Oyesiji Abiodun Abeeb, AlDosari Dalia I, Alghamdi Amani, Aziz Al-Amri Abdul, Ahmad Sarfaraz, Ola Mohammad Shamsul
Biochemistry Department, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia.
Departments of Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Saudi J Biol Sci. 2023 Sep;30(9):103779. doi: 10.1016/j.sjbs.2023.103779. Epub 2023 Aug 18.
Cerebrovascular disease is a threat to people with diabetes and hypertension. Diabetes can damage the brain by stimulating the renin-angiotensin system (RAS), leading to neurological deficits and brain strokes. Diabetes-induced components of the RAS, including angiotensin-converting enzyme (ACE), angiotensin-II (Ang-II), and angiotensin type 1 receptor (AT1R), have been linked to various neurological disorders in the brain. In this study, we investigated how diabetes and high blood pressure affected the regulation of these major RAS components in the frontal cortex of the rat brain. We dissected, homogenized, and processed the brain cortex tissues of control, streptozotocin-induced diabetic, spontaneously hypertensive (SHR), and streptozotocin-induced SHR rats for biochemical and Western blot analyses. We found that systolic blood pressure was elevated in SHR rats, but there was no significant difference between SHR and diabetic-SHR rats. In contrast to SHR rats, the heartbeat of diabetic SHR rats was low. Western blot analysis showed that the frontal cortexes of the brain expressed angiotensinogen, AT1R, and MAS receptor. There were no significant differences in angiotensinogen levels across the rat groups. However, the AT1R level was increased in diabetic and hypertensive rats compared to controls, whereas the MAS receptor was downregulated (p < 0.05). These findings suggest that RAS overactivation caused by diabetes may have negative consequences for the brain's cortex, leading to neurodegeneration and cognitive impairment.
脑血管疾病对糖尿病和高血压患者构成威胁。糖尿病可通过刺激肾素 - 血管紧张素系统（RAS）损害大脑，导致神经功能缺损和脑卒。糖尿病诱导的RAS成分，包括血管紧张素转换酶（ACE）、血管紧张素II（Ang-II）和血管紧张素1型受体（AT1R），已与大脑中的各种神经疾病相关联。在本研究中，我们调查了糖尿病和高血压如何影响大鼠脑额叶皮质中这些主要RAS成分的调节。我们解剖、匀浆并处理了对照、链脲佐菌素诱导的糖尿病、自发性高血压（SHR）和链脲佐菌素诱导的SHR大鼠的脑皮质组织，用于生化和蛋白质印迹分析。我们发现SHR大鼠的收缩压升高，但SHR大鼠与糖尿病 - SHR大鼠之间无显著差异。与SHR大鼠相比，糖尿病SHR大鼠的心跳较慢。蛋白质印迹分析表明，大脑额叶皮质表达血管紧张素原、AT1R和MAS受体。各大鼠组的血管紧张素原水平无显著差异。然而，与对照组相比，糖尿病和高血压大鼠的AT1R水平升高，而MAS受体下调（p < 0.05）。这些发现表明，糖尿病引起的RAS过度激活可能对大脑皮质产生负面影响，导致神经退行性变和认知障碍。
