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ObjectiveTo study the effects of Wendantang on the expression of miRNA-219， N-methyl-D-aspartate receptor 2B （NR2B）， disrupted in schizophrenia 1 （DISC1）， and Ca2+/calmodulin-dependent protein kinase Ⅱγ （CaMKⅡγ） in the frontal lobe of rats with schizophrenia. MethodSixty rats were randomly divided into six groups， namely normal group， model group， high-， medium-， and low-dose Wendantang groups， and clozapine group， with 10 rats in each group. Rats in high-， medium-， and low-dose Wendantang groups were intragastric with 40， 20， and 10 g·kg-1 Wendantang， and the ones in clozapine group were intragastric with 0.02 g·kg-1 clozapine， those in normal and model group were intragastric with equal volume of normal saline， once a day. After 21 days of administration， rats in all groups except for the normal group were injected with 0.6 mg·kg-1 dizocilpine maleate （MK-801） into the left abdominal cavity for inducing acute schizophrenia. The stereotypic behavior and ataxia in rats were scored according to SAMS and HOFFMAN criteria. The morphological changes in the prefrontal cortex were observed by hematoxylin-eosin （HE） staining. The protein expression levels of NR2B, DISC1 and CaMKⅡγ in the frontal lobe was detected by Western blot. The mRNA expression levels of miRNA-219 was detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， the model group exhibited significantly increased stereotypic behavior and ataxia scores （P<0.01）， karyopyknosis and karyolysis in most neurons of the prefrontal cortex， and down-regulated NR2B， DISC1， and CaMKⅡγ protein expression （P<0.01） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression （P<0.01）. Compared with model group， Wendantang high-， medium-， and low-doses group lowered the scores of stereotypic behavior and ataxia at 50， 60 mmin（P<0.05，P<0.01）. In high- and medium-dose Wendantang groups， the neurons in the prefrontal cortex were densely arranged. The karyopyknosis and karyolysis were alleviated to varying degrees. The NR2B protein expression in the frontal lobe was up-regulated （P<0.01）. In the medium- and low-dose Wendantang groups， the DISC1 protein expression in the frontal lobe was up-regulated （P<0.05，P<0.01）. Wendantang at each dose significantly increased the CaMKⅡγ protein expression （P<0.05） and miRNA-219， NR2B， DISC1， and CaMKⅡγ mRNA expression in the frontal lobe （P<0.05，P<0.01）. ConclusionWendantang improves the scores of stereotypical behavior and ataxia， relieves the karyopyknosis and karyolysis of neurons in the prefrontal cortex， and increases the expression levels of miRNA-219， NR2B， DISC1， and CaMKⅡγ of rats with schizophrenia， so as to alleviate the schizophrenic-like symptoms and schizophrenia.
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Objective::To study the effects of Wumeiwan on blood glucose, intestinal microflora, tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and dietary fiber fermented by intestinal microflora in type 2 diabetic (T2DM) rats. Method::Totally 80 SD clean rats were selected as experimental subjects, and 10 of them were randomly selected as the normal group. The remaining 70 rats were given high-sugar and high-fat emulsion for 8 weeks and intraperitoneally injected with streptozotocin (STZ, 35 mg·kg-1) to establish the rat model of T2DM. The fasting blood glucose higher than 11.10 mmol·L-1 was considered as a successful model. The rats that were not successfully modeled were removed, and the remaining rats that were successfully modeled were randomly divided into model group, metformin group, high-dose Wumeiwan group, medium-dose Wumeiwan group and low-dose Wumeiwan group, with 10 rats in each group. Normal group and model group received (ig) normal saline (20 mL·kg-1·d-1), while metformin group (ig metformin 200 mg·kg-1·d-1), Wumeiwan high, medium and low dose groups (ig Wumeiwan 20, 10, and 5 g·kg-1·d-1) received corresponding drugs respectively. Blood glucose and body weight of rats were monitored regularly before and after administration of the drugs. Blood and feces were collected after four weeks of administration.16S-rDNA high-throughput sequencing technology was used for gene sequencing of intestinal flora. Enzyme linked immunoassay (ELISA) was used to detect the serum levels of inflammatory factors TNF-α and IL-10 in rats, and the contents of acetic acid, propionic acid and butyric acid in feces were detected by gas chromatography. Result::As compared with the normal group, the body weight decreased significantly (P<0.01). Bacteroidetes, Actinobacteria, Bacteroides, Clostridium increased, Firmicutes, Deltaproteobacteria, and Lactobacillus decreased, fasting blood glucose and serum TNF-α levels increased significantly (P<0.01), IL-10 level decreased (P<0.01), and the contents of acetic acid, propionic acid and n-butyric acid of short-chain fatty acids decreased(P<0.05, P<0.01) in model group. As compared with the model group, the body weight decreased; Bacteroidetes, Actinobacteria, Bacteroides and Clostridium decreased. Firmicutes, DeltaProteobacteria and Lactobacillus increased; fasting blood glucose and serum TNF-α decreased (P<0.01), and IL-10 increased (P<0.01), contents of acetic acid, propionic acid and n-butyric acid increased in Wumeiwan high-dose, medium-dose and low-dose groups and metformin group (P<0.05, P<0.01). Conclusion::Wumeiwan may prevent and treat T2DM by regulating intestinal flora, improving inflammatory response, increasing SCFAs content and reducing blood glucose.
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Objective:To investigate the effect of Wendantang on cyclic adenosine monophosphate （cAMP）-response element binding protein（CREB） gene silencing hippocampal cell activity， apoptosis and signal pathway of brain-derived neurotrophic factor/protomyosin related receptor kinase B/adenosine cyclophosphate effector binding protein （BDNF/TrkB/CREB）. Method:Wendantang-containing serum was prepared. Animal grouping： SD male rats were randomly divided into high， medium， low-dose groups， clozapine group and normal saline group， with 10 rats in each group， while 15 rats for the normal group. Dosage： 20 mL·kg-1 normal saline was given to normal group N， clozapine 0.02 g·kg-1 was given to dozapine group X， while high， medium and low-dose Wendantang groups were respectively given the same amount of Wendantang concentrated crude drug， with concentrations of 2， 1 and 0.5 g·mL-1 respectively once a day for 8 days continuously， and then blood was taken from femoral artery， and centrifuged for 15 min at 5 000 r·min-1. Supernatant was taken， inactivated， stored at -80 ℃ for standby. The CREB gene silenced hippocampal neuron cell line was constructed through transfection of liposomes into hippocampal cells， and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to verify the effect of small interfering RNA （siRNA） transcription. The mRNA expressions of BDNF， TrkB， CREB and CaMKⅡ in normal hippocampal cells and CREB gene silenced hippocampal cells were measured. Result:Compared with normal group， the apoptosis of the normal gene silencing group was significantly increased （P<0.01）， compared with the normal gene silencing group， the apoptosis of each group was significantly reduced （P<0.01）. As for the mRNA expressions of BDNF， TrkB， CREB and CaMKⅡ， compared with the normal group， the mRNA expression of CREB， BDNF in the normal gene silencing group was significantly decreased （P<0.01）. Compared with the normal gene silencing group， the mRNA expression of BDNF in each administration group was highly increased （P<0.01）， but with no statistically significant difference between TrkB and CaMKⅡ groups. Conclusion:The Wendantang-containing serum could improve the mRNA expression of BDNF， protect hippocampal neurons and prevent cognitive impairment of schizophrenia by regulating BDNF/TrkB/CREB signal pathway.
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Objective To compare the approaches used for the assessment of disability adjust life years (DALYs) for advanced schistosomiasis japonica, so as to provide scientific evidence for accurate assessment of the burden of advanced schistosomiasis japonica. Methods The patients with advanced schistosomiasis japonica receiving treatment and assistance programs in Hunan Province in 2017 were enrolled, and the years lived with disability (YLD) for the patients with advanced schistosomiasis japonica was calculated using the common global burden of disease (GBD) estimation method, the modified GBD method with addition of common syndromes of advanced schistosomiasis japonica, and the quality of life assessment method. Results The YLDs of patients with advanced schistosomiasis japonica, the mean YLDs per capita, and the percentages of YLD were 673.94, 728.77 person-years and 1 761.99 person-years; 0.181, 0.196 person-years and 0.474 person-years; and 10.61, 11.48 person-years per 100 thousand persons and 27.75 person-years per 100 thousand persons with the common GBD method, modified GBD method and the quality of life method, respectively. The YLDs of the patients with advanced schistosomiasis japonica in Hunan Province estimated with the modified GBD method and the quality of life method were 8.14% and 2.61 times higher than that with the common GBD method. Of the major symptoms included in the calculation, the 5 symptoms with the greatest contribution to the burden of advanced schistosomiasis japonica included ascites, moderate anemia, severe anemia, diarrhea and hematochezia. Conclusion The quality of life method may more comprehensively assess the YLDs in patients with advanced schistosomiasis japonica than the common and modified GBD methods.
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Objective To compare the approaches used for the assessment of disability adjust life years (DALYs) for advanced schistosomiasis japonica, so as to provide scientific evidence for accurate assessment of the burden of advanced schistosomiasis japonica. Methods The patients with advanced schistosomiasis japonica receiving treatment and assistance programs in Hunan Province in 2017 were enrolled, and the years lived with disability (YLD) for the patients with advanced schistosomiasis japonica was calculated using the common global burden of disease (GBD) estimation method, the modified GBD method with addition of common syndromes of advanced schistosomiasis japonica, and the quality of life assessment method. Results The YLDs of patients with advanced schistosomiasis japonica, the mean YLDs per capita, and the percentages of YLD were 673.94, 728.77 person-years and 1 761.99 person-years; 0.181, 0.196 person-years and 0.474 person-years; and 10.61, 11.48 person-years per 100 thousand persons and 27.75 person-years per 100 thousand persons with the common GBD method, modified GBD method and the quality of life method, respectively. The YLDs of the patients with advanced schistosomiasis japonica in Hunan Province estimated with the modified GBD method and the quality of life method were 8.14% and 2.61 times higher than that with the common GBD method. Of the major symptoms included in the calculation, the 5 symptoms with the greatest contribution to the burden of advanced schistosomiasis japonica included ascites, moderate anemia, severe anemia, diarrhea and hematochezia. Conclusion The quality of life method may more comprehensively assess the YLDs in patients with advanced schistosomiasis japonica than the common and modified GBD methods.
ABSTRACT
Objective: To research the effect of Wendantang on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/glycogen synthase kinase 3β(GSK3β) signaling pathway of hippocampus in rats with schizophrenia. Method: Sixty SD rats were randomly divided six groups:normal group (A), model group (B), Clozapine group (C), high-dosage group Wendantang (D), medium-dosage Wendantang group (E) and low-dosage Wendantang group (F), with 10 rats in each group. The rats of normal group and model group were given normal saline. The rats of Clozapine group were given 20 mg·kg-1 Clozapine. The rats of high-dosage, medium-dosage, low-dosage Wendantang groups were respectively given 40,20,10 g·kg-1 Wendantang, once a day, for 21 days.Two hours later after the last administration with Wendantang or saline,except for group A, groups B,C,D,E,F were intraperitoneally given MK-801 0.6 mg·kg-1 to establish the rat schizophrenia model. After modeling, the changes in stereotyped behavior of each group were observed and recorded. After three days,the rats were put to death,and the hippocampus tissue were tested. According to Sams Dodd and Hoffman's standard, the stereotyped behavior of rats was scored. The protein expressions of PI3K, Akt and GSK3β of hippocampus were determined by Western blot. The mRNA expressions of PI3K, Akt and GSK3β of hippocampus were tested by Real-time PCR. Result: Compared with A, the stereotyped behavior score of the B was significantly increased (Pβ protein and mRNA of hippocampus were significantly decreased (PPβ protein and PI3K, Akt and GSK3β mRNA of hippocampus (PPConclusion: Wendantang could regulate the PI3K/Akt/GSK3 signaling pathway by improving the stereotyped behavior and increasing the expressions of PI3K, Akt, GSK3β of hippocampus in rats with schizophrenia, so as to achieve the purpose of treating schizophrenia.