Experimental Study Of Lovastatin Inhibiting Inflammatory And Adipogenesis In Thyroid Associated Ophthalmopathy

Objective:1.Fibrocytes are a hot topic in the study of the pathogenesis of TAO.TSHR level from TAO patients is higher than that of healthy controls.After being stimulated by inflammatory cytokines,fibrocytes will also express corresponding inflammatory mediators.Part ? of this article plans to observe the effects of lovastatin on fibrocytes.2.Orbital fibroblasts(OFs)are considered to be the most critical cells involved in the pathogenesis of TAO.They have complex structures and immunoregulatory effects.Studies confirmed that OFs expressed some inflammatory cytokines when stimulated in vitro.The part ? of this article plans to observe the effect of lovastatin on fibroblasts.3.Monocytes have extensive immune regulation,inflammation,and tissue repair functions,and actively participate in the development of many autoimmune disease.Monocytes can secrete a variety of profibrotic factors(TGF-?,PDGF,VEGF)to activate fibroblasts in certain tissues,leading to extracellular matrix deposition and fibrosis.The part ? of this article plans to observe the effects of lovastatin on monocytes.Methods:1.Isolate fibrocytes from the peripheral blood of GD patients and healthy controls,and use Real-time PCR to detect the expression of IL-6 and IL-8 at the gene level after stimulation with TSH;Add lovastatin(1?mol / L)to the sample and observe the effect on TSH-induced high expression of IL-6 and IL-8;Use the “Cocktail method” to induce fibrocytes to differentiate into adipocytes.After oil red O staining,measure the absorbance at 600nm;Observe the effect of lovastatin on PPAR-? gene expression by Real-time PCR.2.Fibroblasts were subcultured from orbital tissue of GD patient and healthy controls.After stimulation with TSH,Real-time PCR was used to detect the expression of IL-6 m RNA and IL-8 m RNA at the gene level;Add lovastatin(1?mol / L)to the sample and observe the effect of lovastatin on TSH-induced high expression of IL-6 and IL-8;Real-time PCR was used to observe the effect of lovastatin on PPAR-? m RNA expression.3.Extract monocytes from the peripheral blood of GD patients and healthy controls and apply Real-time PCR to detect the expression of IL-6 m RNA and IL-8 m RNA at the gene level after stimulation with TSH;Add lovastatin(1?mol / L)to the sample and observe the effect on TSH-induced high expression of IL-6 and IL-8;Observe the effect of lovastatin on inhibiting inflammatory response by comparing dexamethasone with lovastatin.Results:1.TSH can induce increased expression of IL-6 m RNA and IL-8 m RNA gene in bone marrow-derived fibrocytes,its induction effect on GD patients and healthy controls is not significantly different,and the induction effect occurs before translation stage,lovastatin inhibits its expression;Lovastatin inhibits PPAR-? gene expression and fat differentiation of bone marrow-derived fibrocytes.2.TSH can induce the increase of IL-6 m RNA and IL-8 m RNA gene expression in orbital fibroblasts,which has no significant difference in the induction of GD patients and healthy controls.The induction occurs before translation stage.Lovastatin inhibits its expression and the gene expression of PPAR-? m RNA.3.TSH can induce increased expression of IL-6 m RNA and IL-8 m RNA in bone marrow-derived monocytes,and it has no significant difference in the induction of GD patients and healthy controls.The induction occurs before translation stage,lovastatin inhibits its expression;Both dexamethasone and lovastatin can inhibit the inflammatory response.Dexamethasone has a stronger effect than lovastatin.Conclusions:1.lovastatin can inhibit inflammatory of fibrocytes and the differentiation of bone marrow-derived fibrocytes into adipocytes.Lovastatin can inhibit the expression of PPAR-? m RNA.It is speculated that the effect of lovastatin on inhibiting adipocyte differentiation may be achieved through PPAR-? pathway.2.lovastatin can inhibit inflammatory and the expression of PPAR-? gene in orbital fibroblasts.It is speculated that lovastatin may inhibit fat differentiation of orbital fibroblasts by inhibiting the PPAR-? pathway.3.lovastatin can inhibit inflammatory of monocytes.Both dexamethasone and lovastatin can inhibit inflammatory response.Dexamethasone has a stronger effect on inhibiting inflammation than lovastatin.