ABSTRACT
BACKGROUND: Although hypothyroidism during pregnancy may develop grave outcomes for both mothers and offspring, management of which is still a challenge due to the insufficient understanding of this disease. The close correlation between hypothyroidism and preeclampsia is well documented, suggesting that preeclampsia is a potential risk factor for the development of maternal hypothyroidism. However, the exact role of preeclampsia in gestational hypothyroidism is still obscure. OBJECTIVE: In this study, we explored the possible mechanisms of the effect of preeclampsia on thyroid function of maternal rats. METHODS: Thirty pregnant rats were randomly divided into normal pregnancy control (NOP), preeclampsia (PE), and preeclampsia supplemented with amlodipine besylate (PEAml). NG-Nitro-L-arginine-methyl ester was used to induce preeclamptic symptoms. On gestational day 21, rats were sacrificed, and then, the ultrastructure of the thyroid gland, type 1 iodothyronine deiodinase (Dio1) expression, and serum-free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulation hormones (TSH) were assessed. RESULTS: Compared to NOP rats, results of PE rats showed that thyroid follicular cells' ultrastructure was damaged; both hepatic Dio1 mRNA and protein levels were decreased. Interestingly, these changes were ameliorated in PEAml rats. Additionally, FT4, FT3, and TSH levels have no significant differences among groups. CONCLUSION: These findings indicated that preeclampsia could disrupt synthesis, secretion, and metabolism function of thyroid hormones by damaging thyroid follicular cells and interfering Dio1 expression.
Subject(s)
Hypothyroidism/metabolism , Iodide Peroxidase/metabolism , Liver/enzymology , Pre-Eclampsia/metabolism , Thyroid Gland/ultrastructure , Thyroid Hormones/blood , Animals , Female , Hypothyroidism/complications , NG-Nitroarginine Methyl Ester/metabolism , Pregnancy , Pregnancy, Animal , Rats , Rats, Sprague-Dawley , Risk Factors , Thyrotropin/blood , Thyroxine/blood , Time Factors , Triiodothyronine/bloodABSTRACT
Multiple components of traditional Chinese medicine (TCM) formulae determine their treatment targets for multiple diseases as opposed to a particular disease. However, discovering the unexplored therapeutic potential of a TCM formula remains challenging and costly. Inspired by the drug repositioning methodology, we propose an integrated strategy to feasibly identify new therapeutic uses for a formula composed of six herbs, Liuweiwuling. First, we developed a comprehensive systems approach to enrich drug compound-liver disease networks to analyse the major predicted diseases of Liuweiwuling and discover its potential effect on liver failure. The underlying mechanisms were subsequently predicted to mainly attribute to a blockade of hepatocyte apoptosis via a synergistic combination of multiple effects. Next, a classical pharmacology experiment was designed to validate the effects of Liuweiwuling on different models of fulminant liver failure induced by D-galactosamine/lipopolysaccharide (GalN/LPS) or thioacetamide (TAA). The results indicated that pretreatment with Liuweiwuling restored liver function and reduced lethality induced by GalN/LPS or TAA in a dose-dependent manner, which was partially attributable to the abrogation of hepatocyte apoptosis by multiple synergistic effects. In summary, the integrated strategy discussed in this paper may provide a new approach for the more efficient discovery of new therapeutic uses for TCM formulae.
Subject(s)
Apoptosis/drug effects , Databases, Factual , Drugs, Chinese Herbal/pharmacology , Gene Regulatory Networks , Liver Failure/classification , Liver Failure/drug therapy , Systems Biology/methods , Animals , Drug Discovery , Galactosamine/toxicity , Lipopolysaccharides/toxicity , Liver Failure/chemically induced , Liver Failure/genetics , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Signal TransductionABSTRACT
OBJECTIVE: To probe into an effective method for treatment of endometriosis (EMs) and the mechanism. METHODS: Rat EMs model was established and they were randomly divided into a model group, an acup-moxibustion group, a TCM group, an acupuncture and medicine group, with a control group set. The acup-moxibustion group were treated with electroacupuncture at "Xuehai (SP 10)", "Sanyinjiao (SP 6)" and moxibustion at "Guanyuan (CV 4)"; the TCM group were treated with stomach perfusion of modified Mojie Tablet in normal saline; the acupuncture and medicine group were treated with the above two methods; both the control group and the model group were bound and treated with stomach perfusion of saline. After treatment of 35 days, the greatest diameter of the ectopic tissue was measured in the rats, pathological observation of the ectopic tissue was made and matrix metalloproteinase-2 (MMP-2) expression in the ectopic tissue was determined. RESULTS: The greatest diameter of ectopic tissue and MMP-2 expression in the ectopic tissue in the acupuncture and medicine group were significantly lower than those in the model group, the acup-moxibustion group and the TCM group (P < 0.05); and the ectopic endometrium trended to atrophy, and with necrosis of some epithelial cells. CONCLUSION: Combination of acupuncture with medicine has a better therapeutic effect on endometriosis and down-regulates the abnormal increase of MMP-2 level to inhibit the invasion of ectopic tissue to extracellular matrix, so as to reduce the ectopic tissue, hence cure of endometriosis.