Mahadevan P, Larkins R G, Fraser J R, Fosang A J, Dunlop M E
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Diabetologia. 1995 Mar;38(3):298-305. doi: 10.1007/BF00400634.
Exposure in vivo or in vitro to elevated glucose increases production of vasoactive prostaglandins by glomeruli and mesangial cells. This study aimed to determine whether this increased prostaglandin production could provide a link with later structural changes in diabetic nephropathy. Glomerular cores were prepared from control rats and streptozotocin-diabetic rats (3 weeks' duration). Over 24 h in culture hyaluronan production from diabetic glomerular cores was higher than production from control glomerular cores whether maintained in 5.6 mmol/l glucose (105.6 +/- 15.5 vs 53.6 +/- 8.5 ng hyaluronan per 250 glomerular cores, p < 0.001); in 25 mmol/l glucose (149.3 +/- 34.8 vs 62.7 +/- 7.8 ng hyaluronan per 250 glomerular cores, p < 0.01); or in 45 mmol/l glucose (176.8 +/- 23.3 vs 102.0 +/- 17.9 ng hyaluronan per 250 glomerular cores, p < 0.01). At 5.6 mmol/l glucose, exposure in vitro to prostaglandin E2 caused an increase in hyaluronan production [maximal at 10(-9) mol/l prostaglandin E2, 237 +/- 19 vs 42 +/- 4, ng hyaluronan per 250 glomerular cores, p < 0.001 (control) and 195 +/- 7 vs 103 +/- 5, ng hyaluronan per 250 glomerular cores, p < 0.001 (diabetic)]. In both control and diabetic glomerular cores hyaluronan production was reduced significantly by the cyclooxygenase inhibitor indomethacin (10(-5) mol/l) [24.7 +/- 3.33 vs. 40.25 +/- 4.11 ng hyaluronan per 250 glomerular cores, p < 0.05 (control) and 36.5 +/- 6.25 vs 118.0 +/- 22.6, p < 0.01 (diabetic)]. A direct spectrophotometric microassay was used to determine the concentration of sulphated glycosaminoglycans derived from papain-digested glomerular core proteoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
体内或体外暴露于高糖环境会增加肾小球和系膜细胞中血管活性前列腺素的生成。本研究旨在确定这种前列腺素生成增加是否与糖尿病肾病后期的结构变化存在关联。从对照大鼠和链脲佐菌素诱导的糖尿病大鼠（病程3周）制备肾小球核心。在培养24小时期间，无论维持在5.6 mmol/l葡萄糖（每250个肾小球核心产生的透明质酸为105.6±15.5 vs 53.6±8.5 ng，p<0.001）、25 mmol/l葡萄糖（每250个肾小球核心产生的透明质酸为149.3±34.8 vs 62.7±7.8 ng，p<0.01）还是45 mmol/l葡萄糖（每250个肾小球核心产生的透明质酸为176.8±23.3 vs 102.0±17.9 ng，p<0.01）条件下，糖尿病肾小球核心产生的透明质酸均高于对照肾小球核心。在5.6 mmol/l葡萄糖条件下，体外暴露于前列腺素E2会导致透明质酸生成增加[在10(-9)mol/l前列腺素E2时达到最大值，每250个肾小球核心产生的透明质酸为237±19 vs 42±4 ng，p<0.001（对照）以及195±7 vs 103±5 ng，p<0.001（糖尿病）]。在对照和糖尿病肾小球核心中，环氧合酶抑制剂吲哚美辛（10(-5)mol/l）均显著降低了透明质酸的生成[每250个肾小球核心产生的透明质酸为24.7±3.33 vs 40.25±4.11 ng，p<0.05（对照）以及36.5±6.25 vs 118.0±22.6，p<0.01（糖尿病）]。采用直接分光光度微量测定法来测定源自木瓜蛋白酶消化的肾小球核心蛋白聚糖的硫酸化糖胺聚糖浓度。（摘要截断于250字）
