Objective.To observe the protective effect of epigallocatechin gallate (EGCG) on dextran sulfate sodium- (DSS-) induced ulcerative colitis in rats and to explore the roles of TLR4/MyD88/NF-κB signaling pathway.Methods.Rat models of ulcerative colitis were established by giving DSS. EGCG (50 mg/kg/d) was given to assess disease activity index. HE staining was applied to observe histological changes. ELISA and qPCR detected the expression of inflammatory factors. Flow cytometry was used to measure the percentage of CD4⁺IFN-γ⁺and CD4⁺IL-4⁺in the spleen and colon. TLR4 antagonist E5564 was given in each group. Flow cytometry was utilized to detect CD4⁺IFN-γ⁺and CD4⁺IL-4⁺cells. Immunohistochemistry, qPCR, and western blot assay were applied to measure the expression of TLR4, MyD88, and NF-κB.Results.EGCG improved the intestinal mucosal injury in rats, inhibited production of inflammatory factors, maintained the balance of Th1/Th2, and reduced the expression of TLR4, MyD88, and NF-κB. After TLR4 antagonism, the protective effect of EGCG on intestinal mucosal injury was weakened in rats with ulcerative colitis, and the expressions of inflammatory factors were upregulated.Conclusion.EGCG can inhibit the intestinal inflammatory response by reducing the severity of ulcerative colitis and maintaining the Th1/Th2 balance through the TLR4/MyD88/NF-κB signaling pathway.

Background/Aims. Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. Methods. Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL. Oxidative stress and brain injury markers were examined using ELISA. Apoptosis-related proteins and PI3K/AKT/eNOS signaling pathway were determined using western blot assay and immunohistochemistry. Results. EGCG decreased neurological function score, protected nerve cells, inhibited neuronal apoptosis, and inhibited oxidative stress injury and brain injury markers level after MCAO. EGCG reduced the apoptotic rate of neurons, increased the expression of Bcl-2, and decreased the expression of Caspase-3 and Bax. After LY294002 suppressed the PI3K pathway, the protective effect of EGCG decreased after administration of PI3K inhibitors. Conclusion. EGCG has a protective effect on rat brain injury induced by MCAO, possibly by modulating the PI3K/AKT/eNOS signaling pathway.

Objective. This study was aimed at investigating whether sevoflurane inhalation induced cognitive impairment in rats with a possible mechanism involved in the event. Methods. Thirty-two rats were randomly divided into four groups of normal saline (NS) + O₂, NS + sevoflurane (sevo), amyloid-β peptide (Aβ) + O₂, and Aβ + sevo. The rats in the four groups received bilateral intrahippocampus injections of NS or Aβ. The treated hippocampus was harvested after inhaling 30% O₂ or 2.5% sevoflurane. Evaluation of cognitive function was performed by Morris water maze (MWZ) and an Aβ_1–42 level was determined by ELISA. Protein and mRNA expressions were executed by immunohistochemical (IHC) staining, Western blotting, and qRT-PCR. Results. Compared with the NS-treated group, sevoflurane only caused cognitive impairment and increased the level of Aβ_1–42 of the brain in the Aβ-treated group. Sevoflurane inhalation but not O₂ significantly increased glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (IBA)1 expression in Aβ-treated hippocampus of rats. Expression levels for Bcl-xL, caspase-9, receptor for advanced glycation end products (RAGE) and brain-derived neurotrophic factor (BDNF) were significantly different in quantification of band intensity between the rats that inhaled O₂ and sevoflurane in Aβ-treated groups (all P<0.05). Interleukin- (IL-) 1β, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) mRNA expression increased after the rats inhaled sevoflurane in the Aβ-treated group (both P<0.01). There were no significant differences in the change of GFAP, IBA1, Bcl-xL, caspase-9, RAGE, BDNF, IL-1β, NF-κB, and iNOS in the NS + O₂ and NS + sevo group (all P>0.05). Conclusion. Sevoflurane exacerbates cognitive impairment induced by Aβ_1–40 in rats through initiating neurotoxicity, neuroinflammation, and neuronal apoptosis in rat hippocampus.

Objective: To observe the restraining effect of IL-38 on inflammatory response in collagen-induced arthritis rats (CIA), and to explore the regulatory mechanism of SIRT1/HIF-1α signaling pathway. Methods: 40 SD rats were randomly divided into Control group, CIA group, CLL group and CLH group, with 10 rats in each group; CIA rat model was established. The effects of IL-38 on arthritis index, inflammatory response, osteogenic factor and angiogenic factor were observed by methods including HE staining, ELISA, immunohistochemical and immunofluorescence. Human synoviocytes were cultured in vitro, and SIRT1 inhibitors were added to detect the expression for relating factors of SIRT1/HIF-1α signaling pathway by Western blot. Results: IL-38 could alleviate CIA joint damage and restrain inflammatory response, could up-regulate the expression of OPG in CIA rats and could down-regulate the expression of RANKL and RANK. IL-38 could restrain the expression of VEGF, VEGFR1, VEGFR2 and HIF. Moreover, we found that IL-38 could up-regulate the SIRT1 expression and down-regulate the HIF-1α, TLR4 and NF-KB p65 expression in CLL and CLH groups. From the treatment of synoviocytes to simulate the CIA model and the treatment of SIRT1 inhibitors, we demonstrated that the inhibitory effect of IL-38 on inflammatory factors and regulation of SIRT1/HIF-1α signaling pathway-related proteins were inhibited. Conclusion: IL-38 can restrain the inflammatory response of CIA rats, can promote the expression of osteogenic factors, can inhibit neovascularization, and can alleviate joint damage in rats. The mechanism may be related to the regulation of SIRT1/HIF-1α signaling pathway.

Objective. To explore the effect of microRNA-132 of heart failure and provide theoretical guidance for clinical treatment of heart failure (HF). Methods. Peripheral blood was collected from HF patients. RT-qPCR was used to determine microRNA-132 expression. Mouse models of heart failure were established. Color Doppler ultrasound was utilized to measure the changes of cardiac function. HE and Masson staining were applied to observe pathological changes of the myocardium. After H₉C₂ cells were transfected with microRNA-132, MTT assay was employed to detect the stability of H₉C₂ cells. ELISA was used to measure the levels of oxidative stress factors. Western blot assay and RT-qPCR were utilized to determine the expression of Bax, Bcl-2, TGF-β1, and smad3. Results. MicroRNA-132 expression was downregulated in HF patients’ blood. After establishing mouse models of HF, cardiac function obviously decreased. HE staining revealed the obvious edema and hypertrophy of cardiomyocytes. Masson staining demonstrated that cardiomyocytes were markedly fibrotic. After microRNA-132 transfection and H₉C₂ cell apoptosis induced by H₂O₂, antioxidant stress and antiapoptotic ability of the H₉C₂ cells obviously increased. TGF-β1 and smad3 expression remarkably diminished. Conclusion. Overexpression of microRNA-132 dramatically increased the antioxidant stress and antiapoptotic ability of H₉C₂ cells and decreased the expression of TGF-β1 and smad3.

Objectives. We aimed to observe the protective effect of κ opioid receptor (κ‐OR) agonist on myocardial injury in heart failure (HF) rats and its effect on Ca²⁺‐SERCA2a and to explore the regulatory mechanism with the Nrf2/HO‐1 signaling pathway. Methods. 50 Sprague‐Dawley rats were randomly divided into the following groups: the sham operation group (sham group), HF model group (HF group), HF+κ‐OR agonist U50488 group (HU group), HF+U50488H+novel calmodulin‐dependent protein kinase II (CaMKII) agonist (oleic acid) (HUO group), and HF+U50488H+Nrf2 inhibitor (HUM group). The HF rat’s model was established through surgical ligation of the left anterior descending coronary artery and the exhausting swimming exercise. After that, rat’s cardiac function was monitored by echocardiography. HE and MASSON staining was used to detect the myocardial injury, and TUNEL staining was used to detect the myocardial apoptosis. ELISA was performed to detect the biomarkers of oxidative stress. Moreover, the distribution of reactive oxygen species (ROS) and Nrf2 was detected under immunofluorescence. The expression of sarco/endoplasmic reticulum calcium (Ca²⁺) ATPase (SERCA) 2a, calmodulin, endoplasmic reticulum stress‐ (ERS‐) related proteins, and Nrf2/HO‐1 signaling pathway‐related proteins were detected by Western Blotting. Results. κ‐OR agonist U50488H can significantly enhance rat’s cardiac function, reduce the injury and apoptosis of myocardial cells, and alleviate endoplasmic reticulum stress injury in HF rats via upregulating the SERCA2a expression and inhibiting the Ca²⁺ influx. Furthermore, U50488H could also inhibit the phosphorylation of CaMKII and cAMP‐response element binding protein (CREB). Additionally, administration of CaMKII‐specific agonist could partially block the therapeutic effect of κ‐OR agonist on the myocardium of HF rats. Interestingly, the antagonist of Nrf2 could also significantly reverse the therapeutic effect of κ‐OR agonist. Therefore, these results suggested that the effect of U50488H on HF rats is dependent on regulating CaMKII phosphorylation and activating the Nrf2/HO‐1 pathway. Conclusion. κ‐OR agonists U50488H can improve ERS in cardiomyocytes and relieve myocardial injury in HF rats through activating the Nrf2/HO‐1 pathway and regulating Ca²⁺‐SERCA2a to inhibit Ca²⁺ influx.