Soto C, Mena R, Luna J, Cerbón M, Larrieta E, Vital P, Uría E, Sánchez M, Recoba R, Barrón H, Favari L, Lara A
Department of Biological Systems, Metropolitan Autonomous University, Mexico.
Life Sci. 2004 Sep 17;75(18):2167-80. doi: 10.1016/j.lfs.2004.04.019.
Alloxan has been widely used to produce experimental diabetes mellitus syndrome. This compound causes necrosis of pancreatic beta-cells and, as is well known, induces oxidant free radicals which play a relevant role in the etiology and pathogenesis of both experimental and human diabetes mellitus. Previously we have reported hypoglycemic and antilipoperoxidative actions of silymarin in serum and pancreatic tissue respectively. The aim of this study was to test whether silymarin could reduce the hyperglycemia and revert the pancreatic damage in alloxan treated rats, tested with silymarin in two protocols: using both compounds simultaneously for four or eight doses, or using the compound 20 days after alloxan administration for 9 weeks. Serum glucose and insulin were determined, and pancreatic fragments were used for histology and insulin immunohistochemistry. Pancreatic islets were isolated to assess insulin and Pdx1 mRNA expression by RT-PCR. Our results showed that 72 hours after alloxan administration, serum glucose increased and serum insulin decreased significantly, whereas pancreatic tissue presented morphological abnormalities such as islet shrinkage, necrotic areas, loss of cell organization, widespread lipoid deposits throughout the exocrine tissue, and loss of beta cells, but insulin and glucagon immunoreactivity was scattered if any. In contrast the pancreatic tissue and both insulin and glucose serum levels of rats treated with silymarin were similar to those of control animals. In addition, insulin and glucagon immunoreactive cells patterns in Langerhans islets were also normal, and normal insulin and Pdx1 mRNA expression patterns were detected during pancreatic recovery in Langerhans islets. The overall results suggest that silymarin induces pancreatic function recovery demonstrated by insulin and glucagon expression protein and normoglycemia after alloxan pancreatic damage in rats.
四氧嘧啶已被广泛用于诱导实验性糖尿病综合征。这种化合物会导致胰腺β细胞坏死，并且众所周知，它会诱导氧化自由基，而氧化自由基在实验性和人类糖尿病的病因学和发病机制中都起着重要作用。此前我们分别报道了水飞蓟宾在血清和胰腺组织中的降血糖和抗脂质过氧化作用。本研究的目的是测试水飞蓟宾是否能降低四氧嘧啶处理大鼠的高血糖水平并逆转胰腺损伤，采用两种方案用水飞蓟宾进行测试：两种化合物同时使用四剂或八剂，或者在四氧嘧啶给药20天后使用该化合物持续9周。测定血清葡萄糖和胰岛素水平，并将胰腺组织切片用于组织学检查和胰岛素免疫组织化学分析。分离胰岛以通过逆转录聚合酶链反应评估胰岛素和胰腺十二指肠同源盒基因1（Pdx1）mRNA的表达。我们的结果显示，在给予四氧嘧啶72小时后，血清葡萄糖升高而血清胰岛素显著降低，而胰腺组织出现形态学异常，如胰岛萎缩、坏死区域、细胞组织丧失、整个外分泌组织广泛的类脂沉积以及β细胞丢失，但胰岛素和胰高血糖素免疫反应性即使有也很分散。相比之下，用水飞蓟宾处理的大鼠的胰腺组织以及胰岛素和血糖血清水平与对照动物相似。此外，朗格汉斯胰岛中胰岛素和胰高血糖素免疫反应性细胞模式也正常，并且在朗格汉斯胰岛胰腺恢复过程中检测到正常胰岛素和Pdx1 mRNA表达模式。总体结果表明，水飞蓟宾可诱导胰腺功能恢复，这在大鼠四氧嘧啶胰腺损伤后通过胰岛素和胰高血糖素表达蛋白以及血糖正常得以证明。
