TOTAL GLUCOSIDES OF PAEONY ALLEVIATED EARLY RENAL DAMAGE IN DIABETIC RATS BY TLR/MYD88 AND JAK/STAT SIGNALLING PATHWAYS

Xiaoyu Mao¹, Piao Ying², Xiaojun Xu^{2, *}

¹Department of Emergency, East Hospital of Qingdao Municipal Hospital, Qingdao 266071, Shandong Province, China - ²Zhejiang Jinhua Guangfu Cancer Hospital, Jinhua 321000, Zhejiang Province, China

Objective: To analyse the mechanism of total glucosides of paeony on early renal damage in diabetic rats. 

Methods: Ninety clean, healthy male SD rats were randomly selected as control group, model group, TGP low-dose group (low-dose group), TGP high-dose group (high-dose group), TLR/MyD88 signal pathway inhibitor group (TAK242 group) and JAK/STAT signal pathway inhibitor group (AG490 group). The general conditions, 24-hr urinary albumin, endogenous creatinine clearance, urea nitrogen level, renal histopathological changes, oxidation factor level and pathway-related factor level were observed for the rats in each group. 

Results: Compared with the control group, the levels of fasting blood glucose and renal weight/body weight in the model group were significantly higher (P<0.05). Compared with the model group, with the increase of drug dose and concentration, the levels of fasting blood glucose, renal weight/body weight, 24-hr urinary albumin, urea nitrogen, malondialdehyde (MDA), toll-like receptor 4 (p-TLR4), myeloid differentiation factor (p-MyD88), Janus kinase (p-JAK2) and signal transduction nuclear transcription activating factor (p-STAT3) decreased significantly, endogenous creatinine clearance and superoxide dismutase (SOD) After inhibiting the TLR/MyD88 and JAK/STAT signalling pathways, the levels of fasting blood glucose, renal weight/body weight, 24-hr urinary albumin, urea nitrogen, MDA, p-TLR4, p-MyD88, p-JAK2 and p-STAT3 decreased significantly, and the endogenous creatinine clearance rate and SOD level increased significantly. Compared with the control group, the renal tissue of the model group showed obvious glomerular mesangial matrix expansion and glomerular oedema. The capsule narrowed and the positive areas of Schiff's periodate staining increased significantly. The renal tissue of rats in the low-dose and high-dose groups improved in varying degrees, and the improvement was obvious in the high-dose group; after inhibiting TLR/MyD88 and JAK/STAT signal pathway, the renal tissue of the rats improved significantly. 

Conclusion: Total glucosides of paeony can inhibit the increase of blood glucose and inhibit the level of oxidation factor in rats, which may improve the early renal damage in diabetic rats. The mechanism may be related to the inhibition of TLR/MyD88 and JAK/STAT signalling pathway.