Protective effect of 1,25-dihydroxyvitamin D_3 on lung tissues of diabetic rats

Objective To observe the effect of 1,25-dihydroxyvitamin D 3( 1,25-( OH) 2 D 3) on inflammatory level and Toll-like receptor 4( TLR4) expression of lung tissues in diabetic rats,and to investigate the mechanism of the lung protective effect. Methods Ninety SD rats were randomly divided into the control group( group C,n = 10) and diabetic model group( n =80). Streptozotocin( STZ) was injected into caudal veins to generate diabetic models,with 75 diabetic rats generated. Citrate buffer was injected into group C. Seventy-five diabetic rats were randomly divided into five groups( n = 15),including diabetic group( group D),high-dose( group H),medium-dose( group M) and low-dose 1,25-( OH) 2 D 3 intervention groups( group L) and protamine zinc insulin group( group Y). Rats in group H,M and L were administered 0. 3 μg /( kg·d),0. 15 μg /( kg·d),0.025 μg/( kg·d) 1,25-( OH) 2 D 3 intragastrically respectively. Group Y was given 16 U/( kg- 1·d) insulin hypodermic injection in posterior of the neck. Group D and C were given distilled water intragastrically. All rats were sacrificed after 16 weeks by femoral artery hemorrhage. Lung samples were placed in 10% neutral formalin and liquid nitrogen. Blood glucose and serum CRP levels were determined. Pathological alterations in lung tissues were observed through HE and Masson stain. The protein expression of TLR4 and NF-κB p65 was detected by immunohistochemistry. The expression of TLR4,MyD88 and NF-κB p65 mRNA was quantitatively measured by PCR. Results 1. Blood glucose and serum CRP levels were significantly higher in group D than those in group C( P 0. 01),and lower in all intervention groups,especially in group H( P 0. 01). 2. Group D showed severe alveolar wall thickening,significant interstitial proliferation and massive inflammatory cell infiltration. Group H, Y,M and L showed mild to moderate alveolar wall thickening and inflammatory cell infiltration. TLR4 and NF-κB p65 protein expression was significantly higher in all 5 diabetic model groups than that in group C,and significantly lower in group H and Y as compared with that of group D. 3. The expression levels of TLR4,MyD88,and NF-κB p65 mRNA were significantly higher in group D than those in group C( P 0. 01),and lower in all intervention groups as compared with that in group D. TLR4 mRNA expression was positively correlated with both MyD88( r = 0. 610,P 0. 001) and NF-κB p65( r = 0. 744,P 0. 001) mRNA expression. MyD88 and NF-κB p65 mRNA expression was also positively correlated( r = 0. 609,all P 0. 001). Conclusion 1, 25-( OH) 2 D 3 may exert lung protective effect in STZ-induced diabetic rats by down-regulating TLR4-mediated inflammatory pathway.