飲食中添加精胺酸對第 2 型糖尿病大鼠體內發炎反 應及腎損傷之影響

飲食中添加精胺酸對第 2 型糖尿病大鼠體內發炎反 應及腎損傷之影響



，佔總熱量 2%) 取代部分酪蛋白的飼料。以腹腔注射 nicotinamide 及 streptozotocin 的 方式誘發大鼠第 2 型糖尿病。當禁食血糖 ?d 180 mg/dl 即判定為糖尿病。分別在基準 點、 4 週及 8 週時收集血液樣本，並在犧牲時收集腎臟進行分析。研究結果顯示，在 8 週時血漿 C- 反應蛋白 (C-reactive protein, CRP) 、單核球趨化蛋白 (monocyte chemotactic protein, MCP)-1 、前列腺素 (prostaglandin, PG) E2 及果糖胺 (fructosamine) 濃度， DM 及 DM-Arg 組皆顯著高於 NC 組 (p < 0.05) ，且 MCP-1 、 PGE2 在 DM 組與 DM-Arg 組間無統計差異。而血漿 CRP 及 fructosamine 濃度 DM-Arg 組皆顯著低於 DM 組 (CR P: 33.2 ± 4.7 vs. 37.6 ± 4.2 mg/dl, p < 0.05; fructosamine: 0.16 ± 0.02 vs. 0.19 ± 0.02 ΔA/3mi n, p < 0.001) 。在腎臟硝基酪胺酸 (nitrotyrosine) 及核轉錄因子 (nuclear factor-kappa B, N F-κB) 次單元 p65 蛋白質表現結果顯示， DM-Arg 組顯著低於 DM 組 (nitrotyrosine: 17 6 ± 26.7 vs. 199 ± 21 nM, p < 0.05) ，此外，免疫組織染色法得知腎臟 RAGE 表現量， D M-Arg 組亦顯著低於 DM 組 (33.6 ± 0.4 vs. 42.3 ± 0.4 μm2, p < 0.05) 。綜合上述研究結 果顯示，飲食中添加 Arg 對第 2 型糖尿病大鼠可降低血中發炎反應介質，減少體內 AG Es 之合成並改善腎臟損傷之情形。

Effects of dietary arginine on inflammation and renal injury in rats with streptozotocin-induced type 2 diabetes



Arginine (Arg) has been shown to have immunomodulatory effect and inhibits advanced glycation end pro ducts (AGEs) formation in in vitro and in vivo studies. However, the effects of dietary Arg supplementatio n on the expression of inflammatory mediators and renal receptor of AGE (RAGE) in diabetic rats are still unclear. In the present study, normal control (NC) group and two diabetic groups are involved. Rats in NC groups were fed with chow diet. One diabetic group (DM) was fed a common semipurified diet whereas th e other diabetic group received an identical diet except that part of the casein was replaced by Arg (DM-Ar g), which provided 2% of the total energy intake. Diabetes was induced by intraperitoneal injection of nico tinamide followed by streptozotocin. Rats with blood glucose levels exceeding 180 mg/dl were considered diabetic. Blood samples were collected at baseline, 4 wk, and 8 wk. Rats were sacrificed at the end of 8 wk.

The kidneys of the animals were harvested at the end of the study for further analysis. The results showed t

hat plasma C-reactive protein (CRP), monocyte chemotactic protein (MCP)-1, prostaglandin (PG)E2 and fr

uctosamine levels were significantly higher in the diabetic groups than those in the NC group (p < 0.05). N

o differences in plasma MCP-1 and PGE2 levels were found between the DM and DM-Arg groups. Howev

er, CRP, fructosamine were significantly lower in DM-Arg group than in DM group (CRP: 33.2 ± 4.7 vs. 3

7.6 ± 4.2 mg/dl, p < 0.05; fructosamine: 0.16 ± 0.02 vs. 0.19 ± 0.02 ΔA/3min, p < 0.001). Kidney nitrotyro

sine concentrations and nuclear factor-kappa B p65 protein expressions were significantly lower in DM-Ar

g group than in DM group (Nitrotyrosine: 176 ± 26 vs. 199 ± 21 nM, p < 0.05). The result of immunohisto

chemistry stain also showed that the expressions of RAGE in kidney were significantly lower in DM-Arg g

roup than in DM group (33.6 ± 0.4 vs. 42.3 ± 0.4 μm2, p < 0.05). These results suggest that dietary Arg sup

plementation may decrease AGE formation and ameliorate renal damage in rats with type 2 diabetes.