| Background: Sepsis is a clinical syndrome characterised by systemic inflammation due to infection, and the incidence increased year by year,At present, the development of mechanisms are not fully understood. More and more studies show that body oxidative stress peculiar,maybe is one of the important sepsis pathogenesis of liver injury. Nuclear factor E2-related factor 2(nuclear factor-erythroid2-related factor 2, Nrf2) is an important nuclear transcription factor regulator of oxidative stress, It is considered to be a key factor in the body’s regulation of oxidative stress,its may be an important target for the treatment of sepsis liver injury. In sepsis on liver injury,AS- has significant antioxidant Ⅳeffect,it has a strong protective effect, but the exact mechanisms of antioxidant effects are not entirely clear.Objective:To study the therapeutic effect of astragaloside on mitochondrial morphology and the expression of Nrf2 /HO-1 in liver of rat sepsis model of liver injury.Methods: The study includes two parts.(1) 30 rats were divided into 3 groups randomly: Sham operation group, the model group, astragaloside treatment group, 10 rats in each group.Using CLP to establish the rat model of sepsis rat; astragaloside group by intragastric administration 1 h before the operation, at the dose of 50mg/kg, and soluble in sodium carboxymethyl cellulose 1ml, while the remaining two groups only given sodium carboxymethyl cellulose. To observe the symptoms and the survival situation of mice in each group within 24 h.(2): 30 rats were divided into 3 groups randomly(ibid), modeling and intervention treatment ibid, after modeling 6h all survival rats were killed, blood samples were collected and assayed for ALT and AST; Gross morphology of the liver was observed by the naked eye, pathological changes of hepatic tissue were examined by HE staining,and for semi-quantitative analysis.At the same time detected the level of TNF-α, IL-6 in liver tissue, Real-Time PCR was applied for detection of Nrf2, HO-1m RNA expression; Western Blot was applied for detection of Nrf2, HO-1 protein expression. Mitochondrial morphological changes by watching and photographing the transmission electron microscope.Results:(1)Compared with the model group, The survival rats in astragaloside group improved significantly for 24h(0% vs 40%,x2=8.4 P<0.05);serum ALT levels(289.6±62.1 vs 389.5±55.1,p<0.05)and AST levels(609.9±68.0vs916.9±167.5,p<0.05)in rats astragaloside group reduced significantly, liver pathology index improved significantly(13.1±1.6 vs 16.5±1.2,p<0.05);(2)Compared with the model group, TNF-α levels in liver homogenates(682.8±64.9 vs 978.7±110.4,p<0.05)、IL-6 levels(324.8±25.4 vs 602.5±56.9,p<0.05);MDA levels(2.13±0.25 vs 3.24±0.46,p<0.05)、SOD levels(2.85±0.21vs1.63±0.31,p<0.05);liver tissue Nrf2 protein in the cytoplasm relative expression(2043.6±196.9 vs 2875.8±212.0,p<0.01)、Nrf2 nuclear protein relative expression(1490.1±135.8 vs 1452.5±147.0,p<0.01)、HO-1 the relative expression of a protein(7914.8±381.5 vs 3591.1±449.9,p<0.01)and Nrf2 m RNA relative expression levels(30.8±0.7 vs 28.0±0.8,p<0.01),HO-1 m RNA relative expression levels(25.4±0.4 vs 21.7±0.4,p<0.01)were increased significantly in astragaloside group.(3)Compared with the model group, astragaloside hepatic mitochondrial morphology was significantly improved, the severity was significantly lighter than the model group(50% vs 90% x2=6.3,P<0.05)Conclusion: Astragaloside can improve the survival rate and the ALT and AST levels of sepsis-induced liver injury rats,the protection of mitochondrial function in the liver by the enhancement of the Nrf2 /HO-1 pathway.This may be one of the ways by which astragaloside can treat sepsis-induced liver injury. |
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