First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, China.
Exp Clin Endocrinol Diabetes. 2020 Oct;128(10):635-643. doi: 10.1055/a-0635-0672. Epub 2018 Nov 19.
To observe the differences in curative effects between prophylactic and therapeutic administrations of Gliclazide (GLZ) or Methylcobalamin (MCA) on diabetic peripheral neuropathy in rats.
GLZ (25 mg/kg/day) or MCA (175 μg/kg/day) was orally administrated prophylactically to streptozotocin-induced diabetic rats for 8 weeks before diabetic peripheral neuropathy developed or administrated therapeutically after diabetic peripheral neuropathy developed, respectively. The motor nerve conduction velocities (MNCV), aldose reductase (AR) activities, the polyol contents and antioxidative enzyme activities in the sciatic never tissues were determined. The morphology of sciatic never tissues was observed.
In comparison to vehicle, most of the changes in the sciatic nerves of the diabetic rats (e. g., delayed MNCV, altered/damaged nerve structure, enhanced AR activity, increased polyol contents, altered Cu, Zn-superoxide dismutase, glutathione-peroxidase activities, and elevated malondialdehyde level) were significantly ameliorated by prophylactic administration with either GLZ or MCA. In contrast, only few of above-mentioned parameters were alleviated in DPN rats by therapeutic administration with GLZ or MCA as compared to vehicle. The curative effects of GLZ or MCA prophylactic administration on MNCV, AR activity, polyol contents and antioxidative enzyme activities were markedly stronger than therapeutic administration.
Prophylactic administration of GLZ or MCA was superior to the therapeutic administration in alleviation of diabetic neuropathy in STZ-rats, suggesting that pharmacotherapy should be initiated at a much earlier stage before diabetic neuropathy developed, but not at a later stage after never damage reached.
观察格列齐特（GLZ）或甲钴胺（MCA）预防性给药与治疗性给药对糖尿病大鼠周围神经病变疗效的差异。
分别在糖尿病周围神经病变发生前 8 周预防性给予链脲佐菌素诱导的糖尿病大鼠 GLZ（25mg/kg/天）或 MCA（175μg/kg/天），或在糖尿病周围神经病变发生后进行治疗性给药。测定坐骨神经组织的运动神经传导速度（MNCV）、醛糖还原酶（AR）活性、多元醇含量和抗氧化酶活性。观察坐骨神经组织的形态。
与载体相比，糖尿病大鼠坐骨神经的大多数变化（例如，MNCV 延迟、神经结构改变/损伤、AR 活性增强、多元醇含量增加、Cu、Zn-超氧化物歧化酶、谷胱甘肽过氧化物酶活性改变、丙二醛水平升高）均被 GLZ 或 MCA 的预防性给药显著改善。相比之下，与载体相比，GLZ 或 MCA 的治疗性给药仅在少数参数上减轻 DPN 大鼠的上述参数。GLZ 或 MCA 预防性给药对 MNCV、AR 活性、多元醇含量和抗氧化酶活性的疗效明显强于治疗性给药。
GLZ 或 MCA 的预防性给药在改善 STZ 大鼠糖尿病神经病变方面优于治疗性给药，表明药物治疗应在糖尿病神经病变发生之前的更早阶段开始，而不是在神经损伤达到晚期后开始。
