Wendan (温胆) Decoction Regulates Intestinal Flora Disturbance in Rat Model of Schizophrenia
Objective:To investigate the effects of Wendan (温胆) Decoction on the intestinal flora and the expression of short-chain fatty acids (SCFAs),gamma-aminobutyric acid (GABA),5-hydroxytryptamine (5-HT),and dopamine (DA) in the rat model of schizophrenia with in-testinal flora disturbance.Methods:Seventy rats were randomized into normal control,MK-801,MK-801+antibiotics,MK-801+antibiotics+Wendan Decoction (40,20,and 10 g/kg),and MK-801+antibiotics+clozapine (0.02 g/kg) groups,with 10 rats in each group.The rats in drug intervention groups were administrated corresponding drugs by gavage for 21 days,and the antibiotic suspension composed of ampicillin (200 mg/kg),neomycin sulfate (200 mg/kg),metronidazole (200 mg/kg),vancomycin hydrochloride (100 mg/kg) was administrated by gavage for 28 days.The rats in the normal control group and MK-801 group were administrated with the same volume of normal saline.The rats in other groups except the normal control group were modeled for schizophrenia by intraperitoneal injection with 0.6 mg/kg MK-8012 h after the last administration.The stereotyped behavior of rats was observed.The 16S rDNA sequencing was employed to analyze the composi-tion of intestinal flora.The content of SCFAs and neurotransmitters in the frontal cortex was measured by GC-MS/MS and LC-MS/MS,respec-tively.Results:Compared with the normal control group,the MK-801+antibiotics group showed increased stereotyping behavior score after 30 min,decreased number,diversity,and differential species of intestinal flora,reduced content of acetic acid,propionic acid,butyric acid,isobutyric acid,and isovaleric acid (P<0.01),and lowered levels of GABA,5-HT,and DA (P<0.01).Compared with the MK-801+antibi-otics group,drug interventions decreased the stereotyping behavior score (P<0.05).The treatment with Wendan Decoction increased the number,diversity and differential species of intestinal flora and the content of acetic acid,isobutyric acid,and isovaleric acid (P<0.05).The MK-801+antibiotics+Wendan Decoction (40 and 10 g/kg) groups showed increased content of GABA,5-HT,and DA,while the MK-801+antibiotics+Wendan Decoction (20 g/kg) group only showed increased 5-HT content (P<0.05).Conclusion:Wendan Decoction may im-prove the learning and cognitive ability in the rat model of schizophrenia with intestinal flora disturbance by regulating the stereotyped behav-ior,repairing the intestinal flora disturbance,and increasing the content of SCFAs and GABA,5-HT and DA in the brain tissue of the rats trea-ted with MK-801 and antibiotics.
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