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Chronic administration of Ang-(1-7) or A779 STZ induced diabetic rat kidney function

Author: ShaoYing
Tutor: LuLiMin;YaoTai;HuangZuo
School: Fudan University
Course: Physiology
Keywords: STZ induced diabetic rats Renin - angiotensin system Angiotensin 1-7 A779
CLC: R692
Type: Master's thesis
Year: 2007
Downloads: 63
Quote: 0
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Abstract


Renin - angiotensin system (RAS) has an important role in the regulation of the cardiovascular system, cell function, salt and water balance. Past that angiotensin Ⅱ (Ang Ⅱ) the RAS main terminal active product the Ang Ⅱ most. But in recent years, with the development of in-depth study of the RAS and biotechnology, the RAS found a lot of new members, such as angiotensin-converting enzyme 2 (ACE2), renin receptor, Ang-(1-7 ), Ang-(1-7) receptor Mas, and so on. Is the latest confirmed Ang-(1-7) to generate enzyme ACE2 and Ang-(1-7) receptor Mas so that we have a more comprehensive understanding of the RAS: RAS mainly two functions, different members of the different functions, Ang Ⅱ play vasoconstrictor and mitogenic functions, while Ang-(1-7) play a major relaxation of vascular and anti-proliferation function; On the other hand, Ang Ⅱ 2 receptor (AT 2 R )-mediated functions often antagonistic to the Ang Ⅱ 1 receptor (AT 1 R)-mediated functions, and also may be involved in the Ang-(1-7) receptor Mas. In short, the dual role of the RAS can be summed up as a confrontation between the Ang Ⅱ and Ang-(1-7), the confrontation between the AT 1 R AT 2 R and Mas . The pathogenesis of diabetic nephropathy (diabetic nephropathy, DN) has not yet been fully elucidated. Multi-party studies reveal, RAS plays a very important role in the pathogenesis of DN. Is generally believed that the RAS can be divided into the part of the circulating RAS and local RAS not only differences in close contact. DM state, the level of circulating RAS and kidney RAS activity and dynamic changes may be different, even opposite. The purpose of this experiment is to study Ang-(1-7) STZ induced diabetic rat kidney RAS. The experimental observations chronic injection of exogenous Ang-(1-7) and Ang-(1-7) receptor antagonist A779 rat kidney ACE, ACE2, AT 1 R AT R, the MAS and kidney TGF-β expression. The rats were divided into four groups: 1) blank control group; 2) STZ induced diabetic rats group; 3) STZ induced diabetic rats chronic injection of Angiotensin (1-7) group; 4) STZ induced diabetic rat chronic injection A779 group, for 12 weeks. Whole animal data show that Ang-(1-7) administered group renal dysfunction than simply STZ induced diabetic rats group more severe the A779 administered group kidney damage than STZ induced diabetic rats group is serious, but the ratio of Ang-( 1-7), light damage to the administration group. Real-time quantitative PCR results change significantly, Ang (1-7) and A779 the chronic injection group ACE mRNA and ACE2 mRNA levels of Ang-(1-7) and A779 ACE mRNA levels of the administration group compared with STZ diabetic group were significantly elevated , Ang (1-7) group than in A779 group increased more significantly. Ang (1-7) group ACE2 mRNA and protein levels are significantly reduced, while the the A779 group ACE2mRNA and protein significantly increased. Ang (1-7) and A779 injection group angiotensin receptor expression AT 1 R mRNA levels were significantly increased, while AT 2 R MAS receptor mRNA levels were significantly reduced. Western blotting showed no significant difference, STZ induced diabetic group, TGF-β1 protein expression and control group, Ang-(1-7) and A779 groups of TGF-β1 protein expression level was significantly higher, which Ang (1-7) group compared to TGF-β1 expression in A779 group increased more significantly. In summary, the chronic injection of exogenous Ang (1-7) can not improve the STZ-induced diabetic rats kidney damage, but more than A779 accelerate the development of diabetic nephropathy.

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CLC: > Medicine, health > Surgery > Urology ( urinary and reproductive system diseases) > Kidney disease
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