1.Effect of Simiaowan on Promoting Ileal Uric Acid Excretion by Modulating Gut Microbiota to Improve Intestinal Barrier Function and Upregulate ABCG2 Expression in Rats
Yuan ZHANG ; Zhongyou ZHANG ; Huilin FENG ; Lian DUAN ; Lingchun WANG ; Hao DAI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):101-112
ObjectiveTo investigate the effects of Simiaowan on intestinal barrier function and adenosine triphosphate (ATP) binding cassette transporter G2 (ABCG2) expression in hyperuricemic (HUA) rats, and elucidate its therapeutic mechanisms. MethodsForty male Sprague Dawley (SD) rats were randomized into a normal group, a model group, low-dose (282.6 mg·kg-1) and high-dose (565.2 mg·kg-1) Simiaowan groups, and a Benzbromarone (4.7 mg·kg-1) group. The HUA model was established via intraperitoneal injection of potassium oxonate (ip) combined with oral gavage of hypoxanthine (ig) for 14 days. Following modeling, treatments were administered for 14 days. Samples were collected and weighed 4 h after final dosing. Blood uric acid and hepatic function were analyzed. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining, and Chiu's scoring was conducted. Enzyme-linked immunosorbent assay (ELISA) quantified tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), lipopolysaccharide (LPS), diamine oxidase (DAO), and D-lactic acid (D-LA) levels. Real-time polymerase chain reaction (Real-time PCR), Western blot, and immunohistochemistry assessed the expression of Claudin-1, Occludin, occludens-1 (ZO-1), and ABCG2 mRNAs and proteins. 16S rDNA amplicon sequencing characterized ileal microbiota. ResultsCompared with the normal group, the model group exhibited epithelial shedding in the ileal villus, structural disruption, infiltration of extensive inflammatory cells, and significantly elevated Chiu's scores (P<0.01). The DAO, TNF-α, IL-6, IL-1β, LPS, and D-LA levels in the ileum were markedly increased (P<0.01), while mRNA and protein expressions of Claudin 1, Occludin, ZO-1, and ABCG2, as well as positive staining area and proportion, were significantly reduced (P<0.01). Compared with the model group, the Simiaowan groups at all doses showed improved epithelial damage in the ileal villus, significantly lowered Chiu's scores (P<0.01), significantly reduced DAO, TNF-α, IL-6, IL-1β, LPS, and D-LA levels in the ileum (P<0.01), and upregulated mRNA and protein expressions of Claudin 1, Occludin, ZO-1, and ABCG2, as well as positive staining area and proportion (P<0.01). The 16S rDNA results showed that in the model group, the α-diversity index of the ileal microbiota was increased, and species diversity and richness were enhanced, with microbiota dysfunction observed. The community structure of the gut microbiota was significantly different from that of the normal microbiota. The abundance of probiotics was decreased, and the abundance of pathogenic bacteria was increased, with butyrate-producing bacteria showing a low abundance. In contrast, Simiaowan at all doses reduced species diversity and richness, regulated microbiota dysfunction, and promoted the shift of the structure of the gut microbiota community towards a normal one. This increased the abundance of beneficial bacteria, decreased the abundance of harmful bacteria, and restored the abundance of butyrate-producing bacteria. ConclusionSimiaowan enhances ileal uric acid excretion and further alleviates HUA by modulating the gut microbiota composition to improve the intestinal barrier and upregulate the expression of the urate transporter ABCG2 in HUA rats.
2.Atherosclerosis Related Risk Factor Analysis in Middle and Old Age Patients With Newly Diagnosed Type 2 Diabetes Mellitus
Xiaoyang LIU ; Chao LIU ; Taolin ZHENG ; Zhongyou DAI ; Wanhong DU ; Yong ZHANG ; Lijun LIU ; Huaping WAN ; Hui QIN
Chinese Circulation Journal 2016;31(9):874-877
Objective: To study the relationship between serum levels of insulin-like growth factor-1 (IGF-1), cystation-C (Cys-C), interleukin-6 (IL-6) and atherosclerosis in middle and old age patient with newly diagnosed type 2 diabetes mellitus (T2DM). Methods: A total of 206 patients with newly diagnosed T2DM at the age of (67.3±10.4) years were enrolled. Based on color Doppler ultrasound examination, the patients were divided into 2 groups: Control group, the patient without carotid plaque or increased intima thickening, n=105 and Experiment group, patient with carotid plaque or increased intima thickening, n=101. The general information, fasting blood glucose, 2h postprandial blood glucose, glycosylated hemoglobin, LDL-C, HDL-C, TG, TC and IGF-1, Cys-C, IL-6, hs-CRP were recorded and compared between 2 groups, BMI was calculated in all patients. Results: Compared with Control group, Experiment group had increased carotid intima-media thickness (CIMT), elevated serum levels of Cys-C, IL-6, hs-CRP and reduced IGF-1, allP<0.05. Multiple Logistic regression analysis showed that CIMT was negatively related to IGF-1 (r=-0.493,P<0.01), positively related to Cys-C, IL-6 and hs-CRP (r=0.464,r=0.219 andr=0.618, allP<0.01). Conclusion: Serum levels of Cys-C and IL-6 might be the independent risk factors for atherosclerosis occurrence in meddle and old patients with T2DM; combined detection of IGF-1, Cys-C and IL-6 could help clinical diagnosis in relevant patients.

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