Study on intervention of DCP on MAPK signaling pathway to inhibit inflammatory response and alleviate progression of liver fibrosis in rats / 中国药理学通报

Aim To investigate whether DCP has pro- teetive effeet on 2 ,4-dimethylnitrosamine ( DMN) -induced liver fibrosis rat model and its effect on MAPK signaling pathway.Methods Hats were intraperitoneal ly injected with DMN to establish HF model,and then were randomly divided into five groups, namely model group, colchicine group, DCP low-dose, medium-dose and high-dose groups,and control group.The rats were given DMN continuously for six weeks.Serum was col-lected afterwards to detect biochemical indexes of liver function.HE and Masson staining and immunohisto- chemical experiments were performed on liver tissues.RT-PCR was applied to detect the expression of inflammatory factors.Western blot was used to detect the ex pression of proteins related to MAPK pathway,the preventive effect of DCP on HF was observed, and its in-tervention effect on MAPK pathway was explored.Results The liver function of rats in model group was severely impaired, with obvious hepatocyte damage, inflammatory cell infiltration and increased interstitial fibrosis , suggesting that the preparation of HF model was successful.Conclusions DCP can interfere with MAPK signaling pathway to inhibit the inflammatory response and alleviate the progression of HF in rats.

Protective Effect of Gentiopicroside Against Liver Injury in Mice via TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the mechanism of gentiopicroside （GPS） in preventing acute liver injury induced by carbon tetrachloride （CCl₄） in mice and its effect on the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） signaling pathway. Method:Sixty mice were randomly divided into a normal control group， a model group， a silymarin group （150 mg·kg^-1）， and high- （200 mg·kg^-1）， medium- （100 mg·kg^-1）， and low-dose （50 mg·kg^-1） GPS groups， with 10 in each group. The mice in the groups with drug intervention were administered correspondingly by gavage at 10 mL·kg^-1， and those in the normal control group and the model group receive an equal volume of distilled water， once per day. Ten days after administration， mice in the normal control group were subjected to the intraperitoneal injection of peanut oil （10 mL·kg^-1） and those in other groups were injected with peanut oil （10 mL·kg^-1） containing 0.12% CCl₄for the induction of acute liver injury model. After fasting for 16 hours， blood was collected from eyeballs and liver tissues were collected. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of liver tissues. The content or activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， alkaline phosphatase （ALP）， total superoxide dismutase （T-SOD）， and <italic>γ</italic>-glutamyl transpeptidase （<italic>γ</italic>-GT） in the serum， malondialdehyde （MDA） and glutathione peroxidase （GSH-Px） in liver tissues were determined by biochemistry techniques. The levels of tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， and interleukin-6 （IL-6） in liver tissues were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of TLR4， MyD88， and NF-<italic>κ</italic>B in liver tissues. The expression of phosphorylated NF-<italic>κ</italic>B （p-NF-<italic>κ</italic>B） was detected by immunohistochemistry. Result:Compared with the normal control group， the model group showed increased levels of ALT， AST， ALP， TBIL， <italic>γ</italic>-GT， and MDA （<italic>P</italic><0.01）， and blunted activities of T-SOD and GSH-Px （<italic>P</italic><0.01）. Compared with the model group， the high- and medium-dose GPS groups exhibited declining levels of ALT， AST， ALP， TBIL， <italic>γ</italic>-GT， and MDA （<italic>P</italic><0.05， <italic>P</italic><0.01） and potentiated T-SOD and GSH-Px activities （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the normal control group， the model group displayed elevated levels of TNF-<italic>α</italic>， IL-1<italic>β</italic>， and IL-6 in liver tissues （<italic>P</italic><0.01） and increased protein expression of TLR4， MyD88， and p-NF-<italic>κ</italic>B （<italic>P</italic><0.01）. Compared with the model group， the high- and medium-dose GPS groups showed decreased TNF-<italic>α</italic>， IL-1<italic>β</italic>， and IL-6 content in liver tissues （<italic>P</italic><0.05， <italic>P</italic><0.01） and dwindled TLR4， MyD88， and p-NF-<italic>κ</italic>B protein expression （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:GPS possesses a protective effect on mice with acute liver injury induced by CCl₄， and its mechanism of action may be related to the regulation of TLR4/MyD88/NF-<italic>κ</italic>B signaling pathway and inhibition of oxidative stress.

Protective Effect and Mechanisms of Geraniin on D-galactosamine-induced Liver Injury in Mice / 中国实验方剂学杂志

Objective:To explore the hepatoprotective effect and its mechanism of the geraniin on mice with acute liver injury induced by D-galactosamine (D-GalN). Method:A total of 60 Kunming mice were randomly divided into normal group, model group, Silymarin group (positive group 180 mg·kg-1), and low, medium and high-dose geraniin groups (50, 100, 200 mg·kg-1). All the mice were given with saline or corresponding dose of drugs (10 mL·kg-1) by gavage once a day for 10 d. After 2 h of the last administration, except the normal group, the mice of other groups were injected intraperitoneally with D-GalN (500 mg·kg-1) to induce the acute liver injury. After 16 h, the eye balls of mice were removed to take blood, and all mice were put to death to collect samples of liver. Activity or content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) in liver were determined by biochemical method. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), γ-interferon (IFN-γ) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA), and expressions of Toll-like receptor-4(TLR-4) and nuclear factor(NF)-κB proteins were detected by Western blot. Liver histopathological changes were observed by hematoxylin-eosin (HE) staining. Result:Compared with the normal group, the serum levels of ALT, AST, ALP, TBIL and liver MDA in the model group were significantly increased (PPPPPPα, IL-1β, IL-6, IFN-γ and the expressions of TLR-4 and NF-κB proteins in serum (PPConclusion:Geraniin has an obvious protective effective on acute liver injuries induced by D-GalN in mice. Its mechanism may be correlated with oxidative stress, inflammation and TLR-4/NF-κB signaling pathway.

Protective Effect of Formula of Gougancat Decoction on Acute Liver Injury Induced by Carbon Tetrachloride in Rats / 中国实验方剂学杂志

Objective: To explore the protective effect of formula of Gougancai decoction (FGD) on acute liver injury induced by carbon tetrachloride (CCl4) in rats, in order to provide basis for the development of pharmaceutical preparations or healthcare products. Method: Sixty rats were randomly divided into normal group, Silymarin group (120 mg·kg-1) and FGD groups (475, 950, 1 900 mg·kg-1). The normal group and the model group were given equal volume of saline by gavage, while the other groups were administered with the corresponding dose of drugs according to the body weight. After 10 days, the acute liver injury model was established with 12% carbon tetrachloride peanut oil solution (5 mL·kg-1), except the normal group. All of the rats were put to death to collect serum and liver tissues. The contents of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected by biochemical methods, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in liver tissues were determined by enzyme-linked immunosorbnent assay(ELISA). Nuclear factor-κB (NF-κB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expression in liver tissues were detected by Western blot, and htoxylin eosin (HE) staining was used to observe the variation of liver histopathological. Result: Compared with the normal group, the serum activities of AST, ALT, ALP and the content of TBIL, MDA in the model group were significantly increased (Pα, IL-1β, IL-6 in liver tissue were remarkably increased (PPκB was enhanced in liver tissue (Pγ was down-regulated (PPPα, IL-1β, IL-6 (PPκB (PPγ (PPConclusion: FGD has a protective effect on CCl4-induced acute liver injury in rats, and its mechanism may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling pathway, with anti-inflammatory and anti-oxidative effects.

Increasing cardiopulmonary bypass flow volume improves outcome of patient with carotid stenosis undergoing coronary artery bypass grafting / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of increasing cardiopulmonary bypass (CPB) flow volume in improving outcome of patients with carotid artery stenosis performed coronary artery bypass grafting (CABG) procedure.</p><p><b>METHODS</b>Fifty-one patients data collected from January 2006 to March 2008 and divided into two groups (A and B) based on the degree of the carotid artery stenosis diagnosed by ultrasound. Group A included 15 cases with one or both carotid artery stenosis more than 50%, 14 male and 1 female, aged (68.5 +/- 7.7) years old, 14 with hypertension, 2 with diabetes, 6 with myocardial infarction, 3 with cerebral infarction. Group B included 36 cases with stenosis less than 50%, 34 male and 2 female, aged (62.4 +/- 10.2) years old, 28 with hypertension, 7 with diabetes, 20 with myocardial infarction. Increasing CPB flow volume in A group to compare cerebral blood flow (CBF) within procedure in both groups.</p><p><b>RESULTS</b>CPB flow volume in group A was much higher than it in group B (P = 0.001). Mean arterial blood pressure in group A was (67.0 +/- 9.1) mm Hg (1 mm Hg = 0.133 kPa), higher than group B (59.0 +/- 7.1) mm Hg (P = 0.009). There was no significant difference of CBF within procedure and neuropsychologic performance in both group as result.</p><p><b>CONCLUSION</b>For the patients presenting with carotid artery stenosis undergoing the procedure of CABG with CPB, increasing CPB flow volume could improve significantly diseased side cerebral blood flow and might reduce neurological complications.</p>