METHODS: Akita mice were crossbred with NLRP3-/- mice to yield four groups of non-diabetics and diabetics with and without the NLRP3 gene. Females were aged to 30 weeks when Akitas typically exhibit DBD. Urothelia and detrusors were stretched ex vivo to release prostaglandins. Prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) were quantified using enzyme linked immunosorbent assays (ELISA). In separate samples, ex vivo contractile force to PGE2 and PGF2α +/- the prostaglandin F (FP) receptor antagonist, AL8810, was measured. FP receptor protein expression was determined via western blotting.
RESULTS: Stretch-induced PGE2 release increases in urothelia but decreases in detrusors of diabetics. However, PGE2-mediated bladder contractions are not impacted. Conversely, diabetics show no changes in PGF2α release, but PGF2α-mediated contractions increase significantly. This is likely due to signaling through the FP receptors as FP receptor antagonism prevents this increase and diabetics demonstrate a four-fold increase in FP receptor proteins. Without NLRP3-mediated inflammation, changes in prostaglandin release, contractility, and receptor expression do not occur.
CONCLUSIONS: NLRP3-dependent inflammation dysregulates prostaglandin release and prostaglandin-mediated bladder contractions in diabetic female Akita mice via FP receptor upregulation.
方法:秋田小鼠与NLRP3-
结果:拉伸诱导的PGE2释放在糖尿病患者的尿路中增加,但在逼尿肌中减少。然而,PGE2介导的膀胱收缩不受影响。相反,糖尿病患者的PGF2α释放没有变化,但PGF2α介导的收缩显著增加。这可能是由于通过FP受体的信号传导,因为FP受体拮抗作用阻止了这种增加,并且糖尿病患者表现出FP受体蛋白的四倍增加。没有NLRP3介导的炎症,前列腺素释放的变化,收缩性,和受体表达不发生。
结论:NLRP3依赖性炎症通过FP受体上调调节糖尿病雌性秋田小鼠的前列腺素释放和前列腺素介导的膀胱收缩。