RESUMO
ObjectiveTo investigate the protective effect of hepatocyte growth-promoting factor (PHGF) against liver ischemia-reperfusion injury in rats and its mechanism of its action. MethodsA total of 80 healthy male Sprague-Dawley rats were randomly divided into experimental group (PHGF group) and control group (NS group), with 40 rats in each group. A rat model of liver ischemia-reperfusion injury was established by 70% liver ischemia caused by the occlusion of blood flow in the middle and left lobes of the liver, with an ischemia time of 21 minutes. The rats in the PHGF group were given intraperitoneal injection of PHGF for intervention before surgery, and those in the NS group were given an equal volume of normal saline. Serum and liver tissue samples were collected before surgery and on days 1, 3, 5, and 7 after surgery, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) were measured; HE staining was used to observe pathological changes; real-time PCR was used to measure the mRNA expression of mitochondrial transcription factor A (TFAM) in the liver. The independent samples t-test was used for comparison of continuous data between two groups. ResultsHE staining showed that compared with the NS group, the PHGF group had significantly lower degrees of hepatocyte swelling, inflammatory cell infiltration, and hepatocyte necrosis under a light microscope. Liver biochemistry showed that on days 1, 3, 5, and 7 after surgery, the PHGF group had significantly lower serum levels of ALT, AST, and TBil than the NS group (t=11.879, 16.019, 22168, 10.235, 9.041, 12.936, 18.759, 8.142, 10.108, 11.014, 13.245, and 9.968, all P＜0.001). Real-time PCR showed that on days 1, 3, and 5 after surgery, the PHGF group had a significantly higher mRNA level of TFAM in the liver than the NS group (t=7998, 14.764, and 13.861, all P＜0.001). ConclusionPHGF preconditioning exerts a protective effect against liver ischemia-reperfusion injury in rats, possibly by upregulating the expression of TFAM to alleviate liver ischemia-reperfusion injury.
RESUMO
AIM:To investigate effects of resveratrol on mitochondrial DNA copy in retinal vascular endothelial cells cultured under high glucose conditions and its mechanism.METHODS:Human retinal vascular endothelial cells were cultured in low glucose or high glucose medium,the genomic DNA was extracted and copy number of mitochondrial DNA was detected by real-time PCR.Effects of resveratrol on the mitochondrial DNA copy in retinal vascular endothelial cells cultured under high glucose medium were studied.The expression of mitochondrial transcription factor A (TFAM) and acetylated proliferator-activated receptor coactivator-1 alpha (PGC-1α) were analyzed by Western blot and coimmunoprecipitation.RESULTS:High glucose inhibited the copy number of mitochondrial DNA in retinal vascular endothelial cells.However,resveratrol decreased the level of acetylated PGC-1α in retinal vascular endothelial cells,increased the expression of TFAM and the copy number of mitochondrial DNA.CONCLUSION:Resveratrol may improve mitochondrial function of retinal vascular endothelial cells exposed to a high glucose environment via activation of the PCG-1α-TFAM signaling pathway.
RESUMO
Objective To investigate the effect of curcumin pretreatment on the expression of uncoupling protein 2 (UCP2) and mitochondrial transcription factor A (MTFA) in rats' cerebral cortex against focal ischemia reperfusion injury. Methods Eighty male SD rats weighed 220g-300g were randomly divided into 4 groups: sham-operated group, ischemia/reperfusion (I/R) group, curcumine 50mg/kg+I/R (low dose) group, and curcumine 100mg/kg+I/R (high dose) group. The common carotid artery, external carotid artery and internal carotid artery on the right side were exposed in the sham-operated group. Animals of the other groups were subjected to a 2-hour period of right middle cerebral artery occlusion, followed by 24 hours of reperfusion, and then they were sacrificed. Curcumin was administered (ip) in a dose of 50mg/kg (low dose group) or 100mg/kg (high dose group) for 5 days, respectively, prior to arterial occlusion. The pathological changes in neurons and their mitochondria in the cerebral cortex supplied by middle cerebral artery were observed with Nissl staining and electron microscope, respectively. The expressions of UCP2 and MTFA in corresponding cotex were assessed by immunohistochemistry and RT-PCR. Results Compared with sham-operated group, animals in I/R group presented edema of neurons in the corresponding cortex, reduction in the number of Nissl bodies, and swelling of mitochondria with broken, even lysis of cristae. Low dose and high dose of curcumin pretreatment before brain ischemia significantly alleviated the loss of neurons and the damage of mitochondria, accompanied with an increase in the expression of UCP2 and TFAM (P<0.05), and the changes appeared a dose-dependent manner (P<0.05). Conclusions Curcumin may prevent neurons from focal cerebral ischemia reperfusion injury by up-regulating UCP2 and MTFA. Regulation of mitochondrial biogenesis may probably be a potential target of curcumin as a neuroprotective drug.