Nicholls K, Mandel T E
Department of Nephrology, Royal Melbourne Hospital, Parkville, Australia.
Lab Invest. 1989 Apr;60(4):486-91.
The effects of islet isografting and of aminoguanidine on the accumulation of advanced glycosylation end-products (AGE) in renal basement membranes were studied in Streptozotocin (STZ)-induced diabetes mellitus in female BALB/c mice. The characteristic autofluorescence of glycosylated collagen was used to quantitate AGE. We studied the effect of islet isografting using 3 groups of mice, sacrificed at age 13 to 15 months: group A, untreated diabetes (STZ 250 mg/kg intravenously at age 6 to 8 weeks); group B, untreated diabetes for 7 months, then successfully grafted with cultured islet cells; and group C, age-matched normal control animals. At sacrifice, AGE were measured in digests of renal basement membranes as collagen-linked fluorescence/unit of hydroxyproline. Group A animals had significantly greater renal basement membrane glycosylation than did the other 2 groups, (group A median 88.0 arbitrary units/mumol hydroxyproline, range 30.2 to 127.5; group B median 19.4, range 5.1 to 56.8; group C median 2.9 range 0-13.5; p = .001 A versus B). To study the effect of aminoguanidine, 4 groups of animals were used: group 1, untreated diabetics (STZ 250 mg/kg intravenously at age 6 to 8 weeks); group 2, diabetics treated with aminoguanidine 50 mg/kg intraperitoneally daily; group 3, age-matched control animals, and group 4, age-matched controls treated with aminoguanidine. At sacrifice after 7 months, AGE were measured in digests of renal basement membranes as collagen-linked fluorescence/unit of hydroxyproline. Aminoguanidine significantly attenuated the accumulation of AGE in diabetic mice (group 1 median 47.2 arbitrary units/mumol hydroxyproline, range 16.1 to 56.0; group 2 median 24.4, range 5.0 to 37.7; group 3 median 13.6, range 0 to 30.3; group 4 median 10.8, range 2.1 to 17.2; p less than 0.01, groups 1 versus 2). These results indicate that further basement membrane glycosylation is prevented by restoration of euglycemia by islet grafting after a significant duration of diabetes, and that aminoguanidine prevents AGE accumulation despite hyperglycemia.
在雌性BALB/c小鼠中，研究了胰岛移植和氨基胍对链脲佐菌素（STZ）诱导的糖尿病小鼠肾基底膜中晚期糖基化终产物（AGE）积累的影响。利用糖基化胶原蛋白的特征自发荧光来定量AGE。我们使用3组小鼠研究胰岛移植的效果，这些小鼠在13至15月龄时处死：A组，未治疗的糖尿病小鼠（6至8周龄时静脉注射STZ 250 mg/kg）；B组，未治疗糖尿病7个月，然后成功移植培养的胰岛细胞；C组，年龄匹配的正常对照动物。处死时，通过测定肾基底膜消化物中胶原蛋白连接荧光/羟脯氨酸单位来测量AGE。A组动物肾基底膜糖基化程度显著高于其他两组（A组中位数为88.0任意单位/μmol羟脯氨酸，范围为30.2至127.5；B组中位数为19.4，范围为5.1至56.8；C组中位数为2.9，范围为0至13.5；A组与B组相比，p = 0.001）。为了研究氨基胍的作用，使用了4组动物：第1组，未治疗的糖尿病小鼠（6至8周龄时静脉注射STZ 250 mg/kg）；第2组，每天腹腔注射50 mg/kg氨基胍治疗的糖尿病小鼠；第3组，年龄匹配的对照动物；第4组，用氨基胍治疗的年龄匹配的对照动物。7个月后处死时，通过测定肾基底膜消化物中胶原蛋白连接荧光/羟脯氨酸单位来测量AGE。氨基胍显著减轻了糖尿病小鼠中AGE的积累（第1组中位数为47.2任意单位/μmol羟脯氨酸，范围为16.1至56.0；第2组中位数为24.4，范围为5.0至37.7；第3组中位数为13.6，范围为0至30.3；第4组中位数为10.8，范围为2.1至17.2；第1组与第2组相比，p < 0.01）。这些结果表明，糖尿病持续显著时间后，通过胰岛移植恢复正常血糖可防止肾基底膜进一步糖基化，并且氨基胍尽管存在高血糖仍可防止AGE积累。
