Sochor M, Kunjara S, McLean P
Department of Biochemistry, University College, London, U.K.
Biochem Pharmacol. 1988 Sep 1;37(17):3349-56. doi: 10.1016/0006-2952(88)90649-1.
The present study examined the effect of the aldose reductase inhibitor Statil (ICI 128436, ICI, Cheshire, U.K.) on the levels of metabolites and activities of enzymes involved in the glycolysis, polyol pathway and pentose phosphate pathway and on the flux of radioactive glucose through these pathways in kidney of streptozotocin diabetic rats. In kidneys of diabetic rats of 30 days duration the level of sorbitol was increased by +82% and fructose concentration was raised by +42%. After treatment with Statil for 9 days (reversal study) a significant fall in kidney sorbitol concentration and kidney fructose concentration was found. Lactate and UDP-glucose concentrations which were both significantly raised in diabetes by +80% and +23% respectively decreased by 20% after Statil treatment, together with a decline in UDP-glucose dehydrogenase activity. Aldose reductase and sorbitol dehydrogenase activities were also significantly lowered by Statil. In the reversal study there was no significant effect of Statil on the flux of glucose via alternative routes in the kidney cortex. In kidneys of diabetic rats of 9 days duration, the level of sorbitol increased by +61% and the concentration of fructose was raised by +30%. The treatment with Statil (25 mg/kg) from the day of induction of diabetes (prevention study) prevented the accumulation of sorbitol, fructose and UDP-glucose. The increase in the incorporation of radioactive glucose through the pentose phosphate pathway seen in diabetes was less marked in the renal cortex of diabetic rats treated with Statil ab initio.
本研究考察了醛糖还原酶抑制剂Statil（ICI 128436，ICI，英国柴郡）对链脲佐菌素诱导的糖尿病大鼠肾脏中参与糖酵解、多元醇途径和磷酸戊糖途径的代谢物水平及酶活性的影响，以及对放射性葡萄糖通过这些途径的通量的影响。在病程30天的糖尿病大鼠肾脏中，山梨醇水平升高了82%，果糖浓度升高了42%。用Statil治疗9天（逆转研究）后，发现肾脏中山梨醇浓度和果糖浓度显著下降。糖尿病时分别显著升高80%和23%的乳酸和UDP-葡萄糖浓度在Statil治疗后下降了20%，同时UDP-葡萄糖脱氢酶活性也下降。醛糖还原酶和山梨醇脱氢酶活性也被Statil显著降低。在逆转研究中，Statil对肾皮质中葡萄糖经其他途径的通量没有显著影响。在病程9天的糖尿病大鼠肾脏中，山梨醇水平升高了61%，果糖浓度升高了30%。从糖尿病诱导日开始用Statil（25mg/kg）治疗（预防研究）可防止山梨醇、果糖和UDP-葡萄糖的蓄积。糖尿病时可见的通过磷酸戊糖途径的放射性葡萄糖掺入增加在一开始就用Statil治疗的糖尿病大鼠肾皮质中不太明显。
