ABSTRACT
Hepatic ischemia and reperfusion (I/R) injury is a major cause of liver damage during liver transplantation, resection surgery, shock, and trauma. It has been reported that TXNIP expression was upregulated in a rat model of hepatic I/R injury. However, the role of TXNIP in the hepatic I/R injury is little known. In our study, we investigated the biological role of TXNIP and its potential molecular mechanism in the human hepatic cell line (HL7702â¯cells). Using oxygen-glucose deprivation and reoxygenation (OGD/R) to create a cell model of hepatic I/R injury, we found that the mRNA and protein expression levels of TXNIP were upregulated in HL7702â¯cells exposed to OGD/R. TXNIP overexpression remarkably promoted OGD/R-induced cell apoptosis and lactate dehydrogenase (LDH) release, both of which were significantly decreased by TXNIP knockdown. The production of malondialdehyde (MDA) was also increased by TXNIP overexpression, but was reduced by TXNIP knockdown. Moreover, TXNIP overexpression significantly upregulated the phosphorylation of p38 and JNK, which was remarkably inhibited by TXNIP knockdown. Additionally, p38-specific inhibitor SB203580 abrogated the effect of TXNIP overexpression on OGD/R-induced cell injury. Taken together, these results indicated that TXNIP knockdown alleviated hepatocyte I/R injury through preventing p38/JNK pathway activation. Thus, TXNIP might offer a novel potential therapeutic target for the treatment of hepatic I/R injury.
Subject(s)
Carrier Proteins/metabolism , Hepatocytes/metabolism , MAP Kinase Signaling System , Reperfusion Injury/metabolism , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/genetics , Cell Line , Gene Knockdown Techniques , Hepatocytes/drug effects , Humans , Imidazoles/pharmacology , MAP Kinase Signaling System/drug effects , Malondialdehyde/metabolism , Models, Biological , Pyridines/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reperfusion Injury/prevention & control , Reperfusion Injury/therapy , Up-RegulationABSTRACT
Shenqi Fuzheng injection is extracted from the Chinese herbs Radix Astragali and Radix Codonopsis. The aim of the present study was to investigate the neuroprotective effects of Shenqi Fuzheng injection in cerebral ischemia and reperfusion. Aged rats (20-22 months) were divided into three groups: sham, model, and treatment. Shenqi Fuzheng injection or saline (40 mL/kg) was injected into the tail vein daily for 1 week, after which a cerebral ischemia/reperfusion injury model was established. Compared with model rats that received saline, rats in the treatment group had smaller infarct volumes, lower brain water and malondialdehyde content, lower brain Ca(2+) levels, lower activities of serum lactate dehydrogenase and creatine kinase, and higher superoxide dismutase activity. In addition, the treatment group showed less damage to the brain tissue ultrastructure and better neurological function. Our findings indicate that Shenqi Fuzheng injection exerts neuroprotective effects in aged rats with cerebral ischemia/reperfusion injury, and that the underlying mechanism relies on oxygen free radical scavenging and inhibition of brain Ca(2+) accumulation.
ABSTRACT
OBJECTIVE: To study the protective effects of Shenqi Fuzheng Injection (SFI) on cerebral ischemia/reperfusion injured aged rats. METHODS: Aged SD male rats, weighing 200-300 g, were randomly divided into 4 groups: the model group, the sham-operative group, the nimodipine positive control group (abbreviated as nimodipine group) and the SFI group. Focal cerebral ischemia/reperfusion injured rat model was established by modified Longa method. SFI was administered by intravenous dripping 1 week before ischemia. Nervous function disorder, brain infarction area, serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels, brain contents of Ca2+ , water, MDA and SOD levels were observed 3 hrs after ischemia and 3 hrs after reperfusion. RESULTS: perimental results showed that SFI could obviously improve the deficit of nerve function, decrease water content of brain, reduce the infarction area of brain, and inhibit Ca2 + aggregation. LDH and CK levels in serum and MDA in brain were obviously lower than those in the model group and SOD activity in cerebral tissue was obviously higher than that in the model group. CONCLUSION: SFI had protective effect on cerebral ischemia/reperfusion injured aged rats, whose mechanism might be related to the inhibition of lipid peroxidation and Ca2+ aggregation.
