Effects Of Recombinant Globular Adiponectin On Endoplasmic Reticulum Stress And Autophagy In Diabetic Mice

Objective:To observe the effect of recombinant globular adiponectin on the expression of autophagy and endoplasmic reticulum stress in the testis of diabetic mice induced by streptozotocin,and to explore whether recombinant globular adiponectin has a protective effect on the testis of diabetic mice by regulating autophagy and endoplasmic reticulum stress.Methods:Forty-eight male C57BL/6 mice were randomly divided into normal control(NC,n=8)and diabetic(n=40).Diabetic was induced by intraperitoneal injection of streptozotocin.Twenty-four mice were successfully induced.Diabetic mice were randomly divided into three groups: diabetic(DM,n=8),diabetic treated with low-dose of adiponectin(DLA,n=8),and diabetic treated with high-dose of adiponectin(DHA,n=8).Mice in DLA group and DHA group were given intraperitoneal injection of recombinant globular adiponectin at dose of 5μg/(kg.d)and 15μg/(kg·d)respectively.Mice in NC group and DM group were given intraperitoneal injection of the same amount of normal saline.After 8 weeks of adiponectin treatment,blood samples were taken to measure blood glucose,testosterone,LH,FSH and insulin levels.Testicular weight was measured and the ratio of testis weight to body weight was calculated.Sperm count and sperm mobility were measured.Morphological changes of testicular tissues were observed by HE staining.The mRNA expressions of endoplasmic reticulum stress(GRP78,CHOP,caspase-12)and autophagy(LC3,Beclin1 and p62)were determined by real-time PCR.Results:Compared to NC group,seminiferous tubules were deformed,the number of spermatogenic cells and sustentacular cells was reduced,the number of sperm in the tubular lumen was reduced,and spermatogenic cells were sloughing in some tubular lumens in DM group.The body weight,testicular weight,sperm motility,sperm count,and the levels of serum insulin,testosterone,LH and FSH were significantly decreased in DM group compared to NC group(P<0.05).The mRNA expression of Beclin1 and LC3 were significantly decreased(P<0.05),and the mRNA expression of p62,GRP78,CHOP and caspase-12 were significantly increased in the testis of DM group compared to NC group(P<0.05).Recombinant globular adiponectin can significantly reverse the above-mentioned changes in the testis of diabetic mice,and the effect of DHA group was better than that of DLA group.Conclusion:The level of autophaggy was decreased and the level of endoplasmic reticulum stress was increased in the testis of diabetic mice.Recombinant globular adiponectin might produce the protective effect on the testis of diabetic mice by regulating autophagy and endoplasmic reticulum stress.The protective effect of adiponectin is dose-dependent and the high dose is better than the low dose.