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New therapeutic avenue in the fight against chronic liver disease
Hematoxylin and eosin staining, Oil Red O staining and electron microscopy were used to visualize triglyceride accumulation in liver. Furthermore, Liraglutide treatment was found to improve hepatic steatosis. Keywords: glucagon like peptide 1, Liraglutide, nonalcoholic fatty liver disease, insulin resistance, insulin signaling. This work is published and licensed by Dove Medical Press Limited.
By accessing the work you hereby accept the Terms. In addition, a study has evidenced that this pathway exerts crucial effects on the occurrence and development of liver fibrosis 3.
Inflammation is a key factor triggering liver fibrosis and simulating the progression of liver cirrhosis 4. PI3K and mTOR can upregulate anti-inflammatory cytokines, inhibit the expression of pro-inflammatory cytokines, the inflammatory response of liver cells, and the proliferation and invasion of hepatic stellate cells, and promote the degradation of the liver extracellular matrix 5.
A study has demonstrated that astragaloside IV AS-IV , one of the active components of Astragalus saponins in Astragalus membranaceus , has various pharmacological effects such as antioxidation, anti-inflammation and anti-infection 6. According to another study, AS-IV pretreatment can reduce cerebral ischemia-reperfusion injury in rats, which is mainly due to its ability to inhibit neutrophil adhesion-associated molecules, thereby inhibiting inflammation 8.
Recent studies have manifested that AS-IV pretreatment can protect kidney injury, and its mechanisms include reducing inflammation and inhibiting apoptosis 9. The normal control group was intraperitoneally injected with olive oil twice a week, and given intragastric administration of 0. The rats were sacrificed at the end of the 8th week, and underwent solid instead of liquid fasting overnight on the day before the end of the experiment. The next day, the rats were anesthetized, and their abdominal venous blood and liver were taken.
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All the operations were carried out according to the manufacturer's instructions. The fixed liver tissues in each group were selected. These tissues underwent dehydration and transparency at first, immersed in wax and embedded into wax blocks next, and cut into blank slices finally. After the stained slices were dehydrated with gradient alcohol and made transparent via xylene, they were sealed with gum.
Adiponectin Signaling Pathways in Liver Diseases.
Then the histopathological changes in the liver of rats in each group were observed using a microscope Olympus Corp. After the total protein was extracted with the tissue lysate, the protein concentration was determined via BCA assay, and then the proteins were mixed with the loading buffer and underwent thermal denaturation. Then the membrane was transferred through wet processes, and the separated proteins were electrotransferred onto a polyvinylidene difluoride PVDF membrane.
Afterwards, secondary antibody diluted at , were added for incubation at room temperature for 2 h.
The t-test was implemented for the intergroup comparison. There were intact liver lobule structures and central veins in the liver of rats in the normal control group. Destructed liver structures and inflammatory cell infiltration appeared in the liver of rats in the model group, while the above symptoms of rat liver tissues in the AS-IV treatment group were remarkably improved Fig. Compared with the blank control group, obvious collagen hyperplasia was observed in liver tissues of the model group, and the fiber rope formed was relatively thick; whereas collagen deposition in liver tissues in the AS-IV treatment group was significantly reduced compared with that of the model group, and the fiber rope formed was relatively thin Fig.
Detection of the effect of AS-IV on the expression of collagens in liver tissues of rats via Masson's trichrome staining. Liver cirrhosis results from many chronic liver diseases developing to the late stage. The long-term stimulation of damage factors leads to diffuse necrosis of liver cells, and promotes the proliferation of fibrous tissues and the regeneration of nodular hepatocytes, thus ultimately contributing to the remodeling of liver lobule structures and blood vessels A large number of basic and clinical studies have manifested that treatments can reverse the progression of liver fibrosis 11 , A great controversy currently exists in the treatment of liver cirrhosis, and some studies have revealed that early treatment can reverse liver cirrhosis 13 — PI3K phosphorylates phosphoinositides via the phosphorylation of serine and threonine by phosphoinositide-dependent kinase-1 PI3 on the inositol ring generates phosphatidylinositol 4,5-bisphosphate PIP 2 and phosphatidylinositol 3 , 4 , 5 -trisphosphate PIP 3 , and then acts as the second messenger in cells.
According to a study, platelet-derived growth factors can induce the phosphorylation of PI3K and Akt. Activated Akt can promote the phosphorylation of downstream substrates such as mTOR, Bad and the caspase family, having a variety of biological effects Another study has revealed that the mTOR inhibitors, sirolimus and everolimus, can significantly slow the development of liver fibrosis, and inhibit the migration of hepatic stellate cells and the production of collagens The histopathological detection revealed that there were intact liver lobule structures and central veins in the liver of rats in the normal control group.
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Destructed liver structures, inflammatory cell infiltration, and the significant increase in collagen expression appeared in the liver of rats in the model group, while the above symptoms of rat liver tissues in the AS-IV treatment group were remarkably improved, and collagen deposition in liver tissues in the AS-IV treatment group was significantly reduced compared with that in the model group. This study provides a clear research basis for the treatment of liver cirrhosis with AS-IV in clinic.
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RW and HL wrote the manuscript and conducted the experimental animal grouping and treatment. RC analyzed the biochemical indexes.
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YS and TL contributed to western blotting. All authors read and approved the final manuscript. Zhonghua Linchuang Yishi Zazhi.
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