Expression Of Peroxisome Proliferators-activated Receptor γ And Genes Related To Pyroptosis In Lacrimal Gland Under Conditions Of Dry Eye And Diabetes

AIM: To decipher the regulatory roles of the peroxisome proliferator-activated receptor γ(PPARγ)in pyroptosis of lacrimal gland function under conditions of desiccating stress,diabetes or diabetic dry eye.METHODS: One hundred and forty-eight healthy adult male C57BL/6J mice were randomly divided into four groups: a control group,dry eye group,diabetic group and diabetic dry eye group using the random number table.Type 2 diabetes was induced in mice by intraperitoneal injection of streptozocin(STZ)in 0.1 M citrate buffer(p H 6.3).Dry eye was induced in the dry eye group by putting the mice into intelligent drying bellows.Mice in diabetic dry eye group received both of STZ and desiccating stress.Mice all had their phenol red threads test <4mm and fluorescein staining tests >7.The diabetic mice all had blood sugar values >16.7 mmol/L.Mice were kept for ten weeks.Weight,blood sugar,cornea sensitivity,phenol red threads test,fluorescein staining tests of the cornea were measured every week.Six mice were sacrificed every other week and their lacrimal glands removed.We used quantitative polymerase chain reaction(q PCR)to examine the expression of PPARγ interleukin-β(IL-β),Caspase-1 m RNA.We used enzyme linked immunosorbent assay(ELISA)to examine the expression of PPARγ,IL-1β,Caspase-1,nucleotide binding oligomerization domain-like receptors 3(NLRP3)protein.RESULTS: Dry eye mice,diabetic mice,diabetic dry eye mice all showed decreased of cornea sensitivity and tear secretion since the fourth week.Dry eye mice,diabetic mice,diabetic dry eye mice all showed increased of cornea staining since the fourth week.The combined of dry eye and diabetes can lead to more serious lacrimal dysfunction.In the fourth week,the expression of PPARγ m RNA and protein showed no statistical difference among the four groups(P>0.05).The expression of Caspase-1 m RNA and protein showed no statistical difference among the four groups(P>0.05).The expression of IL-1β m RNA and protein showed no statistical difference among the four groups(P>0.05).The expression of NLRP3 protein showed no statistical difference among the four groups(P>0.05).In the sixth week,the expression of PPARγ m RNA showed no statistical difference among the four groups(P>0.05).Relative to normal group,the expression of PPARγ protein had decreased in dry eye group(P<0.05)while diabetes group or diabetes and dry group hadn’t(P>0.05).The expression of Caspase-1 m RNA and protein showed no statistical difference among the four groups(P>0.05).The expression of IL-1β m RNA showed no statistical difference among the four groups(P>0.05).The expression of IL-1β protein showed no statistical difference among normal group,dry group or diabetes group(P>0.05).The expression of IL-1β protein had increased in diabetes and dry group(P<0.05).The expression of NLRP3 protein showed no statistical difference among the four groups(P>0.05).In the eighth week,the expression of PPARγ m RNA showed no statistical difference in dry eye group,diabetic group(P>0.05),relative to the control group.The expression of PPARγ m RNA had decreased in diabetic dry eye group(P<0.05).The expression of PPARγ protein showed no statistical difference in diabetic group(P>0.05),relative to the control group.The expression of PPARγ protein had decreased in dry eye group and diabetic dry eye group(P<0.05).The expression of Caspase-1 m RNA showed no statistical difference in dry eye group,diabetic group and the diabetic dry eye group(P>0.05),relative to the control group.The expression of Caspase-1 protein showed no statistical difference among dry eye group,diabetic group and diabetic dry eye group(P>0.05),relative to the control group.The expression of IL-1β m RNA showed no statistical difference in dry eye group,(P>0.05),relative to the control group.The expression of IL-1β m RNA had increased in dry eye group(P<0.05).The expression of IL-1β m RNA had increased in diabetic dry eye group,(P<0.01).The expression of IL-1β protein showed no statistical difference in diabetic group(P>0.05),relative to the control group.The expression of IL-1β protein had increased in dry eye group and diabetic dry eye group(P<0.05).The expression of NLRP3 protein showed no statistical difference among the four groups(P>0.05).CONCLUSION: 1.Cornea sensitivity of mice and tear secretion was decreased in diabetic group,dry group,diabetic and dry group as time went by,while staining of cornea increased.2.Dry environment and dry environment with diabetes can lead to decrease the expression of PPARγ.Dry environment,diabetes and the combine of the two can all lead to increase of expression of IL-1β.