醛糖还原酶抑制剂泊那司他可防止链脲佐菌素诱导的糖尿病大鼠神经鸟氨酸脱羧酶活性诱导受损。

Impaired induction of nerve ornithine decarboxylase activity in the streptozotocin-diabetic rat is prevented by the aldose reductase inhibitor ponalrestat.

作者信息

Pekiner C, McLean W G

机构信息

Department of Pharmacology and Therapeutics, University of Liverpool.

出版信息

Br J Pharmacol. 1990 Dec;101(4):978-80. doi: 10.1111/j.1476-5381.1990.tb14191.x.

DOI:10.1111/j.1476-5381.1990.tb14191.x

PMID:2128196

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917828/

Abstract

The present study was designed to investigate if the aldose reductase inhibitor ponalrestat is capable of preventing the impairment of the response of ornithine decarboxylase (ODC) to nerve crush in streptozotocin (STZ)-diabetic rats. 2. ODC activity was measured in the dorsal root ganglia of crushed and uncrushed contralateral sciatic nerve of non-diabetic, ponalrestat-treated non-diabetic, STZ-diabetic and ponalrestat-treated STZ-diabetic rats. 3. Twenty four hours after crush, a significant (P less than 0.001) increase in the ratio of ODC activity in ganglia of crushed relative to uncrushed nerves was found in non-diabetic but not in diabetic rats, as expected. In the ponalrestat-treated diabetic rats the ratio was significantly higher (P less than 0.001) than that in the untreated diabetic rats and was not different from that in the non-diabetic group. 4. Ponalrestat also significantly decreased absolute levels of ODC activity in ganglia of uncrushed nerves from diabetic and non-diabetic animals. Despite the near-normal induction of ODC activity by nerve crush in the ponalrestat-treated diabetic animals, absolute ODC activity remained lower than that in ganglia of uncrushed nerves from non-diabetics. 5. We conclude that ponalrestat is able to prevent the impaired induction of ODC in experimental diabetes. The results, however, call into question the relationship between impaired ODC induction and diabetes-induced defects in nerve regeneration, which are insensitive to ponalrestat.

摘要

本研究旨在探讨醛糖还原酶抑制剂泊那司他是否能够预防链脲佐菌素（STZ）诱导的糖尿病大鼠中鸟氨酸脱羧酶（ODC）对神经挤压反应的损害。2. 分别测定了非糖尿病、泊那司他治疗的非糖尿病、STZ诱导的糖尿病以及泊那司他治疗的STZ诱导的糖尿病大鼠中，挤压侧和未挤压侧对侧坐骨神经背根神经节中的ODC活性。3. 挤压后24小时，正如预期的那样，在非糖尿病大鼠中发现挤压侧神经节中ODC活性与未挤压神经的ODC活性之比显著升高（P小于0.001），而糖尿病大鼠中未出现这种情况。在泊那司他治疗的糖尿病大鼠中，该比值显著高于未治疗的糖尿病大鼠（P小于0.001），且与非糖尿病组无差异。4. 泊那司他还显著降低了糖尿病和非糖尿病动物未挤压神经节中ODC活性的绝对水平。尽管在泊那司他治疗的糖尿病动物中，神经挤压后ODC活性诱导接近正常，但ODC活性的绝对水平仍低于非糖尿病动物未挤压神经节中的水平。5. 我们得出结论，泊那司他能够预防实验性糖尿病中ODC诱导受损。然而，这些结果对ODC诱导受损与糖尿病诱导的神经再生缺陷之间的关系提出了质疑，后者对泊那司他不敏感。