Department of Biological Sciences, Faculty of Science, Kuwait University, P.O. Box 5969, 13060 Safat, Kuwait.
Inflammopharmacology. 2013 Apr;21(2):147-59. doi: 10.1007/s10787-012-0139-3. Epub 2012 May 30.
The up-regulation of angiotensin II AT1 receptors has been implicated as a major mediator in the development of hypertension and progressive nephropathy in experimental diabetes. In spite of the documented potential of garlic treatments in ameliorating diabetic complications, the possible involvement of the angiotensin II AT1 receptor, as a central target for the anti-diabetic potential of garlic, has not been explored. Three groups of rats were studied after 8 weeks following diabetes induction: normal, streptozotocin-induced diabetic (control diabetic), and garlic-treated diabetic rats. A polyclonal antibody of proven specificity to the AT1 receptor, as verified by western blotting, indicated in immunohistochemical assays that AT1 receptor labeling was significantly increased in adrenal and renal tissues of control diabetic rats compared to the normal group. The increased AT1 receptor labeling involved all cortical zones and medullary chromaffin cells of the adrenal gland. Except for glomerulii, increased AT1 receptor labeling was also evident in proximal convoluted tubules in the renal cortex, and all tubular segments and interstitial cells outlining the vasa recta bundles in the inner stripe of the outer renal medulla. Compared with control diabetic rats, the labeling of the AT1 receptor in the garlic-treated diabetic group was significantly reduced throughout adrenal and renal regions to levels comparable to those observed in normal rats. The capacity of garlic to modulate diabetes-induced AT1 receptor up-regulation may be implicated in reversing the detrimental consequences of excessive Ang II signaling, manifested by the development of hypertension and nephropathy.
血管紧张素 II AT1 受体的上调被认为是实验性糖尿病中高血压和进行性肾病发展的主要介导因素。尽管大蒜治疗在改善糖尿病并发症方面具有已被记录的潜力,但大蒜作为抗糖尿病潜力的血管紧张素 II AT1 受体的中心靶点的可能性尚未得到探索。在糖尿病诱导后 8 周,研究了三组大鼠:正常组、链脲佐菌素诱导的糖尿病(对照糖尿病)组和大蒜治疗的糖尿病组。一种经过Western blot 验证具有特异性的 AT1 受体多克隆抗体在免疫组织化学检测中表明,与正常组相比,对照糖尿病大鼠的肾上腺和肾脏组织中 AT1 受体标记明显增加。增加的 AT1 受体标记涉及肾上腺的所有皮质区和髓质嗜铬细胞。除了肾小球外,在肾脏皮质的近端卷曲小管中也可以明显看到增加的 AT1 受体标记,并且在肾髓质外带的直小血管束周围的所有管状段和间质细胞中也可以看到增加的 AT1 受体标记。与对照糖尿病大鼠相比,大蒜治疗的糖尿病大鼠的 AT1 受体标记在整个肾上腺和肾脏区域均显著降低,达到与正常大鼠观察到的水平相当。大蒜调节糖尿病诱导的 AT1 受体上调的能力可能与逆转过量 Ang II 信号传递的有害后果有关,表现在高血压和肾病的发展。