| 摘要: | C011-1-Chinese MMP 在老年肥胖症誘發腎臟疾病扮演的角色:1. 血液與腎臟發炎狀態;2 腎纖維 化;3 MMP knock out 機轉 Abstract: 我們初步在老年肥胖腎臟重要發現MMP9 大量提高(如本計劃pilot data)。 老年肥胖症的腎病是常見的問題。此外, 有老年肥胖症的病人當中慢性腎臟病的 盛行率也有偏高現象。發炎狀態，high-mobility group box 1 (HMGB1)，和血漿 metalloproteinases (MMPs)蛋白?的作用與血液透析患者是否伴隨老年肥胖症有 相關目前還不清楚。此外，是否老年肥胖症會引起腎纖維化而造成慢性腎臟病有 待探討，腎纖維化相關途徑是否與matrix metalloproteinases (如MMP-2 和MMP-9) 有關目前仍是未知數。(1/3) 實驗方法: 為了要釐清是否經過長期的間歇性低氧 後血漿中MMP-2, MMP-9, HMGB1 及其他發炎生化指標和會誘發腎臟發炎途徑 在是否有增加的現象，將測試血液biochemical analysis (TG, TC, LDL, HDL, LDH), Inflammatory status (TNF-α, IL-6, IL-10)以及levels of MMP-2, MMP-9, TGF-?1, TIMP-1, and HMGB1 同時比較下列各組小鼠之相關腎組織發炎標記如 NF-kappaB pathway (TNF-α, NFkB, IkB) and Nuclear factor E2-related factor-2 (Nrf2) pathway (MCP-1, NAD(P)H oxidase, cyclooxygenase-2, and 12-lipoxygenase) [G1: lean Zucker rats (n=20 Lean Zucker rats > 1.2 year old); G2: obese Zucker rats(n=20 obese Zucker rats > 1.2 year old)]. (2/3) 實驗方法: 為了要釐清運動治療 療效在老年肥胖症誘發腎臟纖維化，將比較下列各組小鼠之相關腎纖維化標記如 TGF-beta, ERK, MEK, sp1, CTGF, Fibrosis-related MMP-9, MMP-2, TIMP-1, TIMP-2, Fibrosis-related FGF2, u PA, PAI-1 等. [G1: lean Zucker rats (n=20 Lean Zucker rats > 1.2 year old); G2: obese Zucker rats(n=20 obese Zucker rats > 1.2 year old); G3: obese Zucker rats + Swimming exercise 3 month (n=20 obese Zucker rats > 1.2 year old)]. (3/3) 實驗方法:為了要釐清經過運動治療在MMP9 knock out 腎纖 維化和腎纖維化機轉相關途徑,將比較下列各組之腎纖維化和腎纖維化相關途徑 標記,如TGF-beta, ERK, MEK, sp1, CTGF, Fibrosis-related MMP-9, MMP-2, TIMP-1, TIMP-2, Fibrosis-related FGF2, u PA, PAI-1. [G1: normal weight control (n=20 C57BL/6JNarl > 1 year old); G2: high fat diet obesity (n=20 C57BL/6JNarl > 1 year old); G3: MMP-9 knockout mice (n=20 MMP-9 knockout mice > 1 year old); G4: high fat diet in obese MMP-9 knockout mice (n=20 MMP-9 knockout mice); G5: Swimming exercise in MMP-9 knockout mice (n=20 MMP-9 knockout mice); G6: Swimming exercise in obese MMP-9 knockout mice (n=20 MMP-9 knockout mice)].
C011-2-English Title: Role of Exercise therapy and MMP9 in aging obesity-induced kidney diseases: (1/3) renal inflammatory & fibrosis; (2/3) Exercise therapy; (3/3) Exercise therapy in MMP9 knock out mice Abstract: Our preliminary study found MMP9 was upregulated in old obese kidney(shown in pilot data). Patients with end-stage renal disease are commonly seen in aging obesity. Besides, high prevalence of chronic kidney disease was detected among patients with aging obesity. Pro-inflammatory state, high-mobility group box 1 (HMGB1), and plasma MMPs role in hemodialysis patients with aging obesity is still unclear. Furthermore, whether renal inflammatory status, fibrosis and related fibrotic pathway will be enduced in aging obesity and whether renal fibrosis in aging obesity is regulated by matrix metalloproteinases (eg. MMP-9) are not known as well. We intend to study these aspects in this project. (1/3) Method: To clarify whether plasma MMP-2, MMP-9, HMGB1 and inflammatory biomarkers and inflammatory pathways in kidney, biochemical analysis (TG, TC, LDL, HDL, LDH), Inflammatory status (TNF-α, IL-6, IL-10), levels of MMP-2, MMP-9, TGF-?1, TIMP-1, and HMGB1as well as renal NF-kappaB pathway (TNF-α, NFkB, IkB) and renal Nuclear factor E2-related factor-2 (Nrf2) pathway (MCP-1, NAD(P)H oxidase, cyclooxygenase-2, and 12-lipoxygenase) in aging obesity will be compared among the two groups [G1: lean Zucker rats (n=20 Lean Zucker rats > 1.2 year old); G2: obese Zucker rats(n=20 obese Zucker rats > 1.2 year old)]; (2/3) Method: To clarify whether renal fibrosis and related fibrotic pathway will be improved by exercise training, renal Fibrosis-related pathway TGF-beta, ERK, MEK, sp1, CTGF, Fibrosis-related MMP-9, MMP-2, TIMP-1, TIMP-2, Fibrosis-related FGF2, uPA, PAI-1 will be compared among the three groups [G1: lean Zucker rats (n=20 Lean Zucker rats > 1.2 year old); G2: obese Zucker rats(n=20 obese Zucker rats > 1.2 year old); G3: obese Zucker rats + Swimming exercise 3 month (n=20 obese Zucker rats > 1.2 year old)]. (3/3) Method: To clarify whether renal fibrosis and related fibrotic pathway will be further enhanced by high fat-diet MMP-9 knock out mice after exercise training, renal Fibrosis-related pathway TGF-beta, ERK, MEK, sp1, CTGF, Fibrosis-related MMP-9, MMP-2, TIMP-1, TIMP-2, Fibrosis-related FGF2, u PA, PAI-1 will be compared among the six groups [G1: normal weight control (n=20 C57BL/6JNarl > 1 year old); G2: high fat diet obesity (n=20 C57BL/6JNarl > 1 year old); G3: MMP-9 knockout mice (n=20 MMP-9 knockout mice > 1 year old); G4: high fat diet in obese MMP-9 knockout mice (n=20 MMP-9 knockout mice); G5: Swimming exercise in MMP-9 knockout mice (n=20 MMP-9 knockout mice); G6: Swimming exercise in obese MMP-9 knockout mice (n=20 MMP-9 knockout mice)]. |
