Sodium butyrate alleviates pre-eclampsia in pregnant rats by improving the gut microbiota and short-chain fatty acid metabolites production.

AIMS: Pre-eclampsia (PE) affects pregnant patients worldwide, but there is no effective treatment for this condition. We aimed to explore the effect of sodium butyrate (NaB) on PE. METHODS AND RESULTS: In this study, Nω-nitro-L-arginine methyl ester hydrochloride was used to induce PE in pregnant rats. We found that NaB significantly decreased the levels of blood pressure, 24-h protein urine and inflammatory factors (IL-1ß, IL-6 and TGF-ß), increased the foetal and placental weights and intestinal barrier markers (ZO-1, claudin-5 and occludin) expression. In addition, NaB intervention reduced the levels of soluble fms-like tyrosine kinase 1 and soluble endoglin and increased placental growth factor level. Meanwhile, after NaB treatment, the Treg/Th17 ratio of immune cells in the spleen and small intestine of pregnant rats decreased, while the level of pregnancy-related diamine oxidase increased. Notably, the PE rat treatment with NaB improved gut microbiota compositions, especially for the abundances of Firmicutes and Bacteroides, and significantly increased butyric acid and pentanoic acid levels, which might help to alleviate PE in pregnant rats. CONCLUSION: In the PE rat model, exogenous NaB improved intestinal barrier function and reduced adverse outcomes, which might be associated with the gut microbiota and its production of SCFA metabolites. SIGNIFICANCE AND IMPACT OF THE STUDY: NaB might alleviate the adverse outcomes of PE by regulating gut microbiota and its metabolite SCFA, which revealed that NaB might be a potential regulator of gut microbiota and a therapeutic substance for PE.

[Identification of interacting proteins with NF-κB in different status of uterine smooth muscle in labor].

OBJECTIVE: To analyze the differentially expressed proteins which interacted with NF-kappaB in the uterine lower segment smooth muscle tissues under different status of labor onset, and to provide a new foundation on the mechanisms for labor onset.
 Methods: NF-κB P65 protein expression in smooth muscle tissues from the term non-labor group, natural term labor group and drug-induced term labor group was analyzed by Western blot. Co-immunoprecipitation and SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) were performed to detect the proteins interacting with NF-κB p65 in the NF-κB p65 complexes. The components of the complex were identified by LC-ESI-MS/MS (liquid chromatography-tandem electrospray mass spectrometry) and database analysis. The identified differentially expressed proteins were confirmed by Western blot.
 Results: Positive expression of NF-κB was detected in all of the three groups. 10 differentially expressed proteins were identified by LC-ESI-MS/MS in human lower segment myometrium tissues in the term non-labor group and natural term labor group, mean while, 5 differentially expressed proteins were identified in the term non-labor group and the drug-induced labor group. 3 differential expression proteins were detected in all of the 3 groups, including Heat shock 70, Annexin A6 and Desmin, which were verified by Western blot. These proteins were mainly involved in chaperone, signal transduction, cell structure, and energy metabolism process, respectively.
 Conclusion: NF-κB expressed in uterine smooth muscle cells is involved in the process of initiation and regulation of labor onset through a number of proteins relevant to signal transduction, cell structure and energy metabolism.