| Summary: | 碩士 === 國立臺灣大學 === 毒理學研究所 === 106 === Ischemia/reperfusion contributed to most cases of acute kidney injury (AKI), it commonly occurs during kidney transplantation, other major surgery or sepsis. AKI is a severe clinical issue, characterized by kidney damage with a rapid decline of renal function, and strongly associated with high mortality rates. Majority of AKI patients progress to chronic kidney disease (CKD) due to incomplete recovery of AKI further increase the mortality rates in patients. Low intensity pulsed ultrasound (LIPUS) has been recognized to accelerate bone fracture repair process and help in some soft tissues healing such as cartilage and cardiac tissues. However, the effect of LIPUS on renal injury treatment is yet to be investigated. Hence, we aimed to testify the therapeutic effect of LIPUS on renal injury. First, one week before ischemia/reperfusion injury (IRI), we performed unilateral nephrectomy on C57BL/6J male mice, followed by pre-treatment of LIPUS on day 2 after unilateral nephrectomy. IRI surgery was done one week after unilateral nephrectomy, LIPUS treatment was continued started from the day after IRI, once per day until the day of euthanization. Mice sacrificed 24 hours after IRI was considered as AKI model and 30 days after IRI as CKD model. Serum, kidney and bone were harvested for further analysis. By detecting serum biochemical parameter, we observed markedly increase in cystatin C in AKI model and serum creatinine in CKD model after IRI, however, the increase was reduced with LIPUS treatment. Pathological changes of renal tissues was observed using Periodic-Acid Schiff (PAS) stain, results showed less renal injury in IRI+LIPUS group compared to IRI group in CKD model. Besides, with western blot results, we noticed the effect of LIPUS on reducing IRI-induced CHOP and cleaved-caspase 3 expression, implicating decrease in endoplasmic-reticulum(ER) stress, apoptosis and restoring antioxidant enzymes levels such as catalase in AKI and CKD model. Furthermore, the aging markers (p53, p21 and p16) were induced after IRI in CKD model, in contrast LIPUS treatment reversed the situation. We also noted delayed renal fibrosis after IRI with LIPUS treatment by evaluating the fibrosis area on Masson’s Trichrome stained tissue sections and protein expression level of fibrotic marker, α-SMA. Finally, results showed increase of serum FGF23 after IRI declined after LIPUS treatment in CKD model. In short, LIPUS treatment has been demonstrated in our study to exert protective effect on renal injury by attenuating ER stress, apoptosis, restoring antioxidant enzymes, delaying renal aging and renal fibrosis. Therefore, LIPUS could serve as early intervention to reduce renal injury and delay CKD progression.
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