RESUMO
Objective To investigate the effect of fluvastatin on the expressions of caspase-12,CCAAT/enhancer-binding protein homologous protein(CHOP), and c-Jun N-terminal kinases (JNK) in ischemia-reperfusion brain injury in rats.Methods Forty two rats were randomly divided into sham operation group (6 rats), ischemia-reperfusion (I/R) group (18 rats), and fluvastatin (Flu) group (18 rats).The rats of I/R and Flu groups were molded by modified Longa intraluminal thread, then put to death at 2 h occlusion and 24 h reperfusion point.Expressions of caspase-12, CHOP, and JNK were detected with immunohistochemistry and Western blot.Results Immunohistochemistry and Western blot showed that the expressions of caspase-12, CHOP, and JNK were increased at 24 h reperfusion.Compared to I/R group, the expressions of caspase-12 and CHOP in Flu group were decreased significantly (all P ＜0.01);and the expression of JNK had no difference between I/R and Flu groups(P ＞ 0.05).Conclusions The increased expression of caspase-12, CHOP, and JNK showed that endoplasmic reticulum stress was involved in the pathological process of ischemia-reperfusion brain injury.Fluvastatin could inhibit the expression of caspase12 and CHOP, and could delete endoplasmic reticulum stress (ERS) in ischemia-reperfusion brain injury.
RESUMO
Objective To investigate the dynamic changes of endoplasmic reticulum stress-related molecules including glucose regulated protein (GRP78), C/EBP homologous protein (CHOP), and caspase-12 in sciatic nerve of diabetic rats and explore its mechanisms.Methods Rats were randomly divided into normal control group (NC) and diabetes mellitus group (DM) that were induced by intraperitoneal injection of Streptozocin after 4 weeks of high-fat chow feeding.Sciatic nerves were isolated for three times at 4 weeks, 8 weeks and 12 weeks after induction of diabetes.The expressions of GRP78, CHOP,and caspase-12 were detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.The morphology of sciatic nerve was investigated with electron microscope.Results With the extension of the course, demyelinating and axonal injury appeared in sciatic nerve of diabetic rats.The expressions of GRP78 mRNA and protein in DM group were significantly higher than NC group at 4 weeks and 8 weeks after induction of diabetes(P ＜0.05, P ＜0.01).The expressions of CHOP mRNA and protein in DM group were significantly higher than NC group at 8 weeks and 12 weeks after induction of diabetes (P ＜ 0.05).The expressions of caspase-12 mRNA and protein in DM group were significantly higher than NC group at 8 weeks after induction of diabetes(P ＜ 0.05, P ＜ 0.01).Conclusions Endoplasmic reticulum stress-related molecules (GRP78, CHOP, and caspase-12) contributed to the peripheral nerve injury of diabetic rats, and displayed dynamic changes.