Dahuang zhechong pills regulate ASICla/VEGF pathway and alleviate hepatic fibrosis / 中国药理学通报

Aim To examine the therapeutic effects of DHZCP on carbon tetrachloride(CCl4)-induced chemical hepatic fibrosis model in rats and the mechanism of acid-sensitive ion channels 1a(ASIC1a)and vascular endothelial growth factor(VEGF)-related mechanisms.Methods The rats were injected intraperitoneally with CCl4 vegetable oil mixture to establish hepatic fibrosis model,and randomly divided into six groups:control group,hepatic fibrosis model group,DHZCP low dose group,DHZCP medium dose group,DHZCP high dose group and colchicine(Col)positive control group.HE staining was used to observe the pathological changes of hepatic structures in each group,Masson staining to view the production of collagen fibers in each group,and immunohistochemistry,Western blot,q-PCR to investigate the expression level of ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I proteins.Results In model group,serum ALT and AST levels were obviously up-regulated,liver tissue structure was severely damaged,and ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I gene and protein expression levels were significantly elevated.Compared with model group,each treatment group of DHZCP could markedly alleviate the pathological changes of liver fibrosis caused by CCl4,significantly reduce the serum ALT and AST levels,and dose-dependently down-regulate the gene and protein expression levels of ASIC1a,CaMKKβ,VEGF,α-SMA,Collagen-I,etc.Conclusions DHZCP ameliorates hepatic fibrosis in rats,and its mechanism of action may be associated with the regulation of ASIC1a/VEGF.

Acid-sensing ion channels differentially affect ictal-like and non-ictal-like epileptic activities of mouse hippocampal pyramidal neurons in acidotic extracellular pH / 南方医科大学学报

OBJECTIVE@#To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition.@*METHODS@#We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K concentration or the application of an antagonist of GABA receptors in perfusate of mouse hippocampal slices under field potential recordings. We also tested the effects of extracellular acidosis on neuronal excitability under field potential recording and evaluated the changes in epileptic activities of the neurons in response to pharmacological inhibition of ASICs using a specific inhibitor of ASICs.@*RESULTS@#Extracellular acidosis significantly suppressed epileptic activities of the hippocampal neurons by converting ictal-like epileptic activities to non-ictal-like epileptic activities in both high [K ]o and disinhibition models, and also suppressed the intrinsic excitability of the neurons. ASICs inhibitor did not antagonize the inhibitory effect of extracellular acidosis on ictal epileptic activities and intrinsic neuronal excitability, but exacerbated non-ictal epileptic activities of the neurons in extracellular acidotic condition in both high [K]o and disinhibition models.@*CONCLUSIONS@#ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.

Effect of intestinal flora on expression of acid-sensitive ion channel 3 in rats and their regulation in intestinal motility in children with functional constipation / 中华实用儿科临床杂志

Objective@#To investigate the effect of intestinal flora in children with functional constipation (FC) on expression of acid-sensitive Ion channel 3(ASIC3) in rats and their regulation in intestinal motility.@*Methods@#Faeces of FC children identified according to RomeⅣ criteria and healthy children from the First Affiliated Hospital of Anhui Medical University from December 2017 to June 2018 were collected, and then made into fecal microbiota solution.A pseudo - sterile rat model was established, according to the random number table method, and the rats were randomly divided into the treatment group and the control group, with 12 rats in each group, then the treatment group was given fecal microbiota solution of the children with FC and the control group was given fecal microbiota solution of the healthy children.The visceral sensitivity and intestinal propulsion rate of rats were determined by means of abdominal withdrawal reflex (AWR), while the intestinal microorganism of rats and children with FC were determined by 16SrDNA high-throughput sequencing, and the expressions of ASIC3 of intestinal in mRNA and protein were determined by adopting fluorescence quantitative PCR and Western blot.@*Results@#The species and quantity of intestinal flora of the children with FC and rats implanted with FC faecal bacteria were reduced(all P<0.05), and firmicutes and bacteroidetes were the main bacteria; compared to the control group, the small intestine propulsion rate(52% vs.74%) and visceral sensitivity(78 mmHg vs.63 mmHg) of the treated group were significantly decreased compared with those in the control group (all P<0.05); the mRNA (0.003 1±0.000 8 vs.0.012 4±0.002 5) and protein levels of ASIC3 (0.013 2±0.001 9 vs.0.072 1±0.008 7) in the small intestine were down-regulated significantly(all P<0.05); and the mRNA (0.002 8±0.000 7 vs.0.009 4±0.001 1) and protein levels of ASIC3(0.038 2±0.004 5 vs.0.089 7±0.009 4) in the colon were down-regulated significantly(all P<0.05).@*Conclusions@#Children with FC have intestinal flora disorder, and intestinal flora of FC children may affect intestinal motility by down-regulating the expression of intestinal ASIC3 in rats.