The role of lipoprotein-associated phospholipase A2 in acute kidney injury of septic mice

Abstract

Background: This experiment aimed to investigate the role and mechanism of lipoprotein-associated phospholipase A2 (Lp-PLA2) in kidney injury in septic mice induced by cecal ligation and perforation (CLP).Methods: Male BALB/c mice were randomly divided into two groups: sham-operation group (Sham group) and septic group (CLP group). The septic model was simulated by cecal ligation and puncture method, but only cecal ligation was used for the sham operation group. The whole serum and renal tissue samples of the mice were collected 24 hours after modeling in both groups. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of renal tissue, the renal injury score was recorded, and the creatinine (Cr) and blood urea nitrogen (BUN) levels were detected by automatic biochemical analyzer, while the serum Lp-PLA2 level was detected by enzyme-linked immunosorbent assay (ELISA). The 7-day survival rate and the survival curve of the two groups were statistically analyzed.Results: Compared with the Sham group, the pathological score of renal injury in the CLP Group was higher, the level of Lp-PLA2 in serum was significantly increased (all P<0.01), and the expression of Lp-PLA2 in renal tissue was significantly elevated (all P<0.01). Furthermore, the 7-day survival rate of the Sham group was 90%, while that of CLP group was 25%. Conclusions:The expression level of Lp-PLA2 in blood and kidney tissue of septic mice was increased and correlated with prognosis. However, the predictive value of Lp-PLA2 for prognosis in septic mice needs further study.

NUCLEOLIN PROTECTS CARDIOMYOCYTES BY UPREGULATING PGC-1α AND PROMOTING MITOCHONDRIAL BIOGENESIS IN LPS-INDUCED MYOCARDIAL INJURY

“…In our previous studies, we found that NCL played important protective effects on cellular injuries induced by oxidative stress and myocardial ischemia-reperfusion injury (24)(25)(26). Recently, it has been reported that NCL exerted a substantial influence on septic cardiomyopathy, and its overexpression proved to have a protective effect on mitochondrial oxidative stress in septic mice (19). Here, we explored how NCL protects mitochondrial biogenesis in LPS-induced myocardial injury by regulating certain specific molecules.…”

“…Previous studies in our laboratory have shown that Tg mice with NCL overexpression have protective effects against myocardial injury and were resistant to mitochondrial oxidative damage (19). Therefore, we also constructed a NCL overexpression model in cells.…”

“…Our previous studies have proved that the expression of NCL in myocardium can be upregulated. The myocardial specific overexpression of NCL can alleviate cardiac dysfunction caused by oxidative stress in septic mice, of which the mortality rate was also decreased (19). However, the exact underlying mechanisms that how NCL protects against the septic cardiomyopathy remain poorly understood.…”

Forsythiaside B ameliorates coagulopathies in a rat model of sepsis through inhibition of the formation of PAD4-dependent neutrophil extracellular traps

“…Histopathological changes in the rats from each group were observed under a light microscope. Tissue injury scores in the lung ( Matute-Bello et al, 2011 ), liver ( Hart, N. et al, 2004 ) and kidney ( Liang et al, 2020 ) were evaluated based on previously published methods.…”

View of the Renin-Angiotensin System in Acute Kidney Injury Induced by Renal Ischemia-Reperfusion Injury

“…RIRI is the leading cause of acute kidney injury (AKI), which is characterized by a sudden decline in renal function, glomerular filtration rate (GFR) reduction, accumulation of nitrogen waste products, and inability to maintain fluid and electrolyte homeostasis [4][5][6]. Molecular mechanisms underlying RIRI-induced AKI are not fully understood, but it has been reported that several factors such as ATP depletion, reactive oxygen species (ROS) production, phospholipase activation, neutrophil infiltration, and release of vasoactive peptides contribute to the pathogenesis of renal damage [7][8][9][10]. Among the diverse mediators that take part in AKI induced by RIRI, the renin-angiotensin system (RAS) plays an important role [11][12][13].…”