ABSTRACT
AIM:To investigate the effect of irbesartan on the fatty liver of db/db mice and whether autophagy is involved in the process.METHODS:Male db/db mice(n=24)were randomly divided into model group and irbesar-tan group,and 12 db/m mice with similar age and weight were selected as normal control group.After 16 weeks of inter-vention respectively,the fatty liver-related parameters including body weight, liver index, blood lipid, liver function and pathological changes in the liver were observed.The protein levels of p-PI3K,p-Akt,and p-mTOR,as well as Atg-7,bec-lin-1 and LC3B in the liver tissues were detected by Western blot,and the autophagosomes in the liver were observed under electron microscope.RESULTS:Compared with the model group,the body weight,liver index,blood lipids,alanine and aspartate aminotransferase were decreased in irbesartan group(P<0.05).Moreover,the pathological changes in the liver were significantly ameliorated in irbesartan group than that of model group.Importantly, the protein levels of p-PI3K, p-Akt and p-mTOR were decreased with irbesartan administration,while the expression of Atg-7,beclin-1 and LC3B-Ⅱwas increased(P<0.05),which resulted in a distinct increase in autophagosomes.CONCLUSION:Irbesartan alleviates he-patic steatosis in db/db mice by inhibiting the PI3K/Akt/mTOR signaling pathway and upregulating the protein expression of Atg-7,beclin-1 and LC3B-Ⅱ,thereby inducing autophagy in hepatocytes.
ABSTRACT
Objective To investigate the effect of eosinophils(EOS)in asthmatic guinea pigs airway and explore the mechanism of antiasthma by inhaled arsenic trioxide. Methods The guinea pigs asthma models were established with ovalbumin(OVA)challenge method,2 groups received inhaled different doses of arsenic trioxide,and three control groups respectively received normal saline inhaled and high dose of arsenic trioxide by intraperitoneal injection and dexamethasone(DEX)intraperitoneally. EOS invaded and apoptosis with all of the groups were assessed after 7 days intraperitoneal injection or inhalation. Results Compared with group of inhaled normal saline, both EOS invaded and apoptosis in bronchus submuconsa were significantly different(P0.05)among groups of inhaled low dose arsenic trioxide [2.0 mg(kg?d)]and intraperitoneal injection with higher dose arsenic trioxide[5.0 kg/(kg?d)]and DEX[10 mg/(kg?d)]for these two parameters. Conclusions The mechanism of arsenic trioxide antiasthma with arsenic trioxide can decrease EOS amount in bronchial submucosa and accelerate EOS apoptosis, and relieve bronchial inflammation in asthma. For inhaled lower dose arsenic trioxide or intraperitoneal injection with high dose arsenic trioxide ,the effect of EOS is equivalent. The antiasthma effect of inhaled lower dose arsenic trioxide[2.0 mg/(kg?d)]is equivalent to intraperitoneal injection higher dose[5.0 mg/(kg?d)],and may be safe comparatively. The mechanism of antiasthma by inhaled arsenic trioxide is the same with DEX.