OBJECTIVE

2

To study the improvement effects and its mechanism of catalpol on testicular lesions in KK-Ay spontaneous diabetic mice on the basis of glycolysis process mediated by advanced glycation end products （AGEs） and their receptors （RAGE）.

METHODS

2

KK-Ay spontaneous diabetic mice fed with high-fat diet were used as diabetic model， and then randomly divided into model group， catalpol group （100 mg/kg）， aminoguanidine group （AGEs inhibitor， 100 mg/kg） and FPS-ZM1 group （RAGE inhibitor， 1 mg/kg）， and C57BL/6J mice fed in the same period were set as normal group， with 6 mice in each group. The catalpol group and aminoguanidine group mice were given relevant medicine intragastrically， normal group and model group mice were given constant volume of normal saline intragastrically， and FPS-ZM1 group mice were given relevant medicine 1 mL/g intraperitoneally， for consecutive 8 weeks. After the last administration， the body mass， fasting blood glucose， 24-hour food intake， water consumption， urine volume， testicular organ coefficient， and sperm motility of the mice were measured； pathological morphology and ultrastructural structure of testicular tissue were observed； the levels of reduced glutathione （GSH）， superoxide dismutase （SOD）， lactate dehydrogenase （LDH） and sugar metabolites in testicular tissue of mice were detected； pathway enrichment analysis was performed； the level of AGEs in serum and testicular tissue， protein expressions of RAGE， B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）， and mRNA expressions of key rate-limiting enzymes [hexokinase （HK）， phosphofructose kinase （PFK）， pyruvate kinase （PK）， LDH] in testicular tissue were all detected.

RESULTS

2

Catalpol could significantly improve the general symptoms， testicular organ coefficients and motility of sperm in KK-Ay spontaneous diabetic mice （

P

＜0.05 or

P

＜0.01）. The morphology and ultrastructure of spermatogenic cells in each layer of the seminiferous tubules were all improved. The levels of GSH， SOD and LDH in testicular tissue，the levels of the metabolic product glucose fructose-1，6-diphosphate， 3-phosphate glycerate， 3-phosphate glyceraldehyde， lactic acid and pyruvate， the expressions of HK， PFK， PK and LDH mRNA were all significantly increased（

P

＜0.05 or

P

＜0.01）； the levels of AGEs in serum and testicular tissue， the expression of RAGE protein and the ratio of Bax to Bcl-2 in testicular tissue were significantly decreased（

P

＜0.05 or

P

＜0.01）. Aminoguanidine and FPS-ZM1 could significantly improve the levels of most of above indicators in mice（

P

＜0.05 or

P

＜0.01）.

CONCLUSIONS

2

Catalpol shows significant improvement effects on testicular lesions of KK-Ay spontaneous diabetic mice， and its mechanism of action was associated with upregulation of AGEs/RAGE signaling pathway-mediated glycolysis.