RESUMO
BACKGROUND: Recent reports have demonstrated that impaired barrier function and local microinflammation in the duodenal mucosa contribute to the pathogeneses of functional dyspepsia (FD). Thus, restoring normal barrier integrity becomes a potential therapeutic strategy in the treatment of FD. Sini-San (SNS) is a traditional Chinese prescription that exhibits therapeutic effects in FD, but the underlying mechanisms remain not well understood. METHODS: FD rats were established by tail clamping method and the therapeutic effect of SNS was evaluated by measuring the visceral sensitivity and gastric compliance. Transepithelial electrical resistance (TEER) that reveals epithelial barrier integrity was measured by Ussing chamber. The expression of tight junction (TJ) proteins, occludin and claudin-1, in the duodenum was determined by Western blot and immunofluorescence. The amount of tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) in duodenal mucosa was detected by enzyme-linked immune sorbent assay (ELISA). The mRNA level of transient receptor potential vanilloid type 1 (TRPV1) was measured by quantitative real time-polymerase chain reaction (qPCR). RESULTS: SNS could improve gastric compliance and attenuate visceral hypersensitivity (VH) in FD rats. TEER was decreased in FD rats, but treatment with SNS restored normal level of TEER and the expression of occludin and claudin-1 in FD rats. In addition, SNS administration ameliorated FD-associated increase in the production of TNF-α, IFN-γ and the expression of TRPV1. CONCLUSIONS: The therapeutic effect of SNS on FD is at least partially through improvement of TJ integrity and attenuation of FD-associated low-grade inflammation in the duodenum. Our findings highlight the molecular basis of SNS-based treatment of FD in human patients.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Dispepsia/tratamento farmacológico , Junções Íntimas/efeitos dos fármacos , Animais , Claudina-1/genética , Claudina-1/metabolismo , Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Dispepsia/genética , Dispepsia/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Masculino , Ocludina/genética , Ocludina/metabolismo , Ratos , Ratos Sprague-Dawley , Junções Íntimas/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the expression of Kisspeptin protein and activities of the hypothalamic-pituitary-ovarian axis(HPOA) in rats with Letrozole-induced polycystic ovary syndrome (PCOS). METHODS: Female SD rats were randomly divided into normal control, PCOS model and EA groups (n=6 rats in each group). The PCOS model was established by continuous gavage of letrozole for 21 d. EA(2 Hz/100 Hz, 0.6-1.4 mA) was applied to bilateral "Daimai" (GB26) for 20 min, once every day for 15 d. Body mass was measured every 4 days. Serum follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and testosterone (T) were detected by radioimmunoassay. Histopathological changes of the ovarian were observed after H.E. staining, and the expression level of Kisspeptin protein in the hypothalamus was detected by Western blot. RESULTS: Following modeling, the body mass, serum T and LH contents, hypothalamic Kisspeptin protein expression and the number of ovarian follicles were significantly increased (P<0.05, P<0.01), while the number of ovarian corpus luteum was apparently decreased in comparison with the normal group (P<0.01). After EA intervention, the serum T, LH and E2 contents, the expression of Kisspeptin protein and the number of ovarian follicles were notably down-regulated (P<0.05, P<0.01), and the number of corpus luteum was significantly increased (P<0.01) in comparison with the model group. CONCLUSION: EA can regulate the levels of sex hormones and HPOA of PCOS rats, which may be related to its effect in down-regulating the expression of Kisspeptin protein in the hypothalamus.