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OBJECTIVE@#To clarify the anti-depressive potential mechanisms of Kaixin Powder (KP), a drug that helps to prevent and treat depression and other mentaldiseases, from genome-wide transcriptome profiling.@*METHODS@#Transcriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats, then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays. Furthermore, high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis.@*RESULTS@#Transcriptome results revealed that the 24 differentially expressed genes (DEGs) in chronic mild stress (CMS) rats could be reversed after two weeks of KP treatment. The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules, including lipid metabolism, synapse function and inflammation. KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms. Furthermore, it was validated that cholesterol metabolism dysfunction can be ameliorated by KP, which was correlated with upregulation of the AdipoR1-BDNF (brain-derived neurotrophic factor) co-regulatory pathway.@*CONCLUSION@#Taken together, our results demonstrated that KP not only alleviates depression via traditional mental illness targets, but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics.
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Objective To observe the role of lycopene played in the liver ischemia reperfusion injury,and its effort on autophagy.Methods Eighty SPF male SD rats(Animal Laboratory of the Yang Zhou University) were divided into 4 groups by random number table.Sham-operated group:after anesthesia,just opened the abdominal cavity.Treatment group:after molding,lycopene (10 mg/kg) was dissolved in medicinal corn oil (2 ml/kg) and intraperitoneal injection was performed.The lycopene was injected 60 minutes before surgery.Control group:after molding,intraperitoneal injection of equal volume of normal saline was given.Inhibiting group:lycopene (10 mg/kg) + 3-ma (15 mg/kg) were injected into the abdominal cavity after injection.20 rats in each group.The determination of sample collection and observation of indicators at 1 h,6 h,12 h,24 h after ischemia reperfusion.The serum ALT and AST levels were checked.The mRNA expression of TNF-α and IL-6 was measured by real-time PCR and the expression of Beclin-1,was detected by western blotting.Hematoxylin and Eeosin staining was used to evaluate the pathological change of liver tissues.The measurement data were expressed as (Mean ± SD),comparisons between the two groups were analyzed by independent sample t test,and comparisons among groups were analyzed by One-way anova and Newman-keuls method.Results The serum ALT levels of Sham-operated group in 1 h,6 h,12 h,24 h were (39.81 ±13.54),(39.65 ±14.24),(39.61 ±13.68),(38.72± 12.85) U/L,the serum ALT levels of liver ischemia-reperfusion control group in 1 h,6 h,12 h,24 h were (128.43 ± 33.49),(637.26 ± 89.53),(289.76 ± 43.59),(124.26 ± 35.32) U/L.Compared with Shamoperated group,the serum ALT levels of liver ischemia-reperfusion control group were significantly increased (P ＜ 0.05).The serum ALT levels of treatment group in 1 h,6 h,12 h,24 h were (73.26 ± 23.24),(419.27 ± 56.49),(196.23 ± 26.23),79.76 ± 20.43) U/L.Compared with liver ischemia-reperfusion control group,the serum ALT levels of treatment group were significantly declined (P ＜ 0.05).The serum ALT levels of inhibiting group in 1 h,6 h,12 h,24 h were (142.59 ±42.86),(592.45 ±48.36),(268.23 ±42.36),(131.23 ± 24.36) U/L.Compared with treatment group,the serum ALT levels of treatment group were significantly increased (P ＜ 0.05).Compared with liver ischemia-reperfusion control group,the serum AST levels and the expression of inflammatory factor TNF alpha and IL-6 of treatment group were significantly declined(P ＜ 0.05).The results of light microscope indicated that treatment groups significantly reduce the liver cell damage compared with liver ischemia-reperfusion control group.The lycopene could promote the autophagy of mice which related to protein of Beclin-1.Drugs of 3-ma which inhibit autophagy,reduces the expression of Beclin-1.Conclusion Lycopene preconditioning can protect liver from ischemia reperfusion injury by promoting autophagy in liver cells.
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Objective To explore the protective effect of astilbin in hepatic ischemia-reperfusion injury (HIRI).Methods SD rats were divided into Sham group (control group),HIRI group (ischemia-reperfusion group),astilbe (low dose group,middle dose group,high dose group),and estabilished the model of rat HIRI.After liver were reperfused with blood (in 4 h,8 h,16 h),collecting the specimens of blood and liver tissues.Detection of serum alanine aminotransferase (ALT),aspertate aminotransferase (AST);Then observed the changes of liver cell microstructure;Western blot analysised the expression of HMGB1,TLR4,NF-kB,TNF-α in liver tissue.Results The serum ALT levels of Sham group in 4 h,8 h,16 h were (58.11 ±4.81) U/L,(57.12 ± 5.33) U/L,(57.63 ±4.54) U/L,the serum ALT levels of HIRI group in 4 h,8 h,16 h were (540.38 ± 21.41) U/L,(831.21 ± 20.11) U/L,(191.95 ± 15.35) U/L.Compared with Sham group,the serum ALT levels of HIRI group were significantly increased(P ＜ 0.01).Compared with HIRI group,The serum ALT levels of three dose groups in 4 h,8 h,16 h were significantly declined,including high dose group lower the most obvious (The serum ALT levels of high dose group in 4 h,8 h,16 h were (223.75 ± 10.53) U/L,(412.14 ±23.59) U/L,(205.25 ± 15.48) U/L (P ＜0.01).The results of light microscope indicated that drug groups significantly reduce the liver cell damage.The results of Western blot displayed that High dose group of HMGB1,TLR4 protein expression in 4 h,8 h,16 h drop significantly than HIRI group(P ＜0.05).High dose group of NFkB,TNF-α protein expression in postoperative 8 h,16 h decrease significantly than HIRI group (P ＜ 0.05),but in postoperative 8 h,there was no statistically significant difference compared with group HIRI (P＞0.05).Conclusion Astilbe pretreatment can reduce HIRI and its mechanism may be associated with downregulating the axis of HMGB1/TLR4/NF-kB/TNF-α,proceed to the next inhibiting the inflammatory response.
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Ischemia-reperfusion injury (IR) refers to the ischemic tissues or organs to regain perfusion on tissue and organ damage.The reactive oxygen species(ROS)generated by the mitochondrial and the change of the mitochondrial permeability can be induced mitophagy.And dysfunction of the mitophagy is closely related to the body a variety of disease.This article aims to introduce the research of progress about mitophagy in recent years,especially the role it play in the ischemia-reperfusion injury.