ABSTRACT
Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM2.5 group, and an SAL+PM2.5 group, each containing 10 mice. In the SAL group and the SAL+PM2.5 group, the mice were administered SAL (60 mg·kg−1) by gavage, while in the control group and the PM2.5 group, sterile saline (10 mL·kg−1) was administered by gavage. In the PM2.5 group and the SAL+PM2.5 group, PM2.5 suspension (8 mg·kg−1) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg−1) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM2.5 group, and finally, the three groups clustered with the PM2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased. Compared to the control group, the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM2.5 group, the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM2.5 group (P<0.05). Conclusion Exposure to PM2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.
ABSTRACT
Objective To investigate the effects of dextran sulfate on lung ischemia-reperfusion injury after lung transplantation in rats.Method A total of 32 male Wistar rats were subjected to unilateral left lung orthotopic transplantation.They were randomly divided two groups (n =16 each):DXS group [DXS (10 mg/kg) was given prior to the reperfusion],and the control group (the same volume of normal saline was given).After animals were sacrificed,the lung graft was harvested 2 h after reperfusion.Oxygenation indexes,wet/dry ratio (W/D),myeloperoxidase (MPO) activity,malondialdehyde (MDA) and endothelin 1 (ET-1) in the transplanted lung,and tumor necrosis factor a (TNF-α) and interleukin 8 (IL-8) in serum were measured.The lung injury scores were evaluated and complement deposition was observed.Result After 2-h reperfusion,compared to the control group,oxygenation indexes were improved significantly in DXS group (P＜0.05),but there were no significant differences in W/D between two groups.In DXS group,the activity of MPO was significantly reduced,and the contents of MDA and ET-1 in the lung tissue were significantly reduced as compared with the control group.DXS reduced the level of TNF-α and IL-8 markedly in serum (P ＜0.05).There was no significant difference in lung injury score between two groups (4.53 ± 0.46 vs.5.28 ±0.49,P＞0.05).Compared to the control group,DXS reduced the deposition of C3c (0.8 ±0.2vs1.5±0.3) andC6 (1.2±0.4vs.2.4±0.5) (P＜0.05).Conclusion Administration of DXS attenuated ischemia-reperfusion injury after lung transplantation by inhibiting complement deposition,and improved the oxygenation of the transplanted lung.This protection was associated with inhibition of inflammation and oxidation and endothelial cytoprotection.
ABSTRACT
Objective To investigate the role of protein kinase C (PKC) in reduction of hepatic ischemiareperfusion injury by CO2 preconditioning in rats.Methods Forty-eight male Wistar rats,aged 8-10 weeks,weighing 230-270 g,were randomly divided into 3 groups (n =16 each):hepatic ischemia-reperfusion injury group (group HIRI),CO2 preconditioning group (group P),and c helerythrine (CHE,a specific inhibitor of PKC) group (group CHE).The portal vein,hepatic artery and bile duct of the left lateral and median lobes of the liver were occluded for 1 h,followed by 4 h reperfusion in anesthetized rats.The rats inhaled 50％ O2-50％ N2 for 1 h during mechanical ventilation in group HIRI.In P group,the rats inhaled 50％ O2-45％ N2-5％ CO2 for 1 h during mechanical ventilation and then inhaled 50％ O2-50％ N2 and the hepatic ischemia-reperfusion injury was performed 15 min later.In group CHE,CHE 5 mg/kg was injected intraperitoneally at 10 min before mechanical ventilation,and the other procedures were similar to those previously described in P group.Before mechanical ventilation,immediately before ischemia,and at 0,1,2,3 and 4 h of reperfusion,mean arterial pressure (MAP) was recorded and arterial blood samples were obtained for blood gas analysis.At 4 h of reperfusion,the serum aspartate amino transferase (AST) and alanine amino-transferase (ALT) activities and tumor necrosis factor-α (TNF-α) concentration (by ELISA) were determined and hepatic specimens were obtained for detection of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (by spectrophotometry),and the expression of activated caspase-3 (by immuno-histochemistry) and PKC (by Western blot) in hepatic tissues.Apoptosis index was calculated by using TUNEL.Results Compared with group HIRI,MAP,PaO2 and PaCO2were significantly increased immediately before ischemia and during reperfusion in group P,MAP and PaCO2 were increased during reperfusion and PaO2 was increased immediately before ischemia and during reperfusion in group CHE,the serum ALT and AST activities,TNF-α concentrations,MDA content and apoptosis index were decreased,and the expression of activated caspase-3 was down-regulated in P and CHE groups,and the SOD activity was increased,and the expression of PKC was up-regulated in group P (P ＜ 0.05 or 0.01),and no significant changes were found in the SOD activity and PKC expression in CHE group (P ＞ 0.05).Compared with group P,MAP was significantly increased immediately after onset of reperfusion,while decreased at 1-4 h of reperfusion,PaO2 was decreased immediately before ischemia and during reperfusion,PaCO2 was decreased at 3 h of reperfusion,the serum ALT and AST activities,TNF-α concentrations,MDA content and apoptosis index were increased,and the expression of activated caspase-3 was up-regulated,and the expression of PKC was downregulated in group CHE (P ＜ 0.05).Conclusion PKC is involved in reduction of hepatic ischemia-reperfusion injury by CO2 preconditioning in rats.