angiotensin-i and Escherichia-coli-Infections

Acute respiratory distress syndrome (ARDS), one of the serious form of acute lung injury (ALI), is the primary cause of death in patients with ALI. Sini decoction (SND) is a widely used Traditional Chinese Medicine (TCM). However, the application of SND in ALI is rarely reported. Previous studies have found that renin-angiotensin-aldosterone system (RAAS) played vital and bidirectional roles in ALI. Therefore, the aim of the present study was to investigate protective effect of SND on ALI model induced by E. coli, as well as to further explore relations between RAAS and SND.. The ALI model was evaluated by morphological observations and biochemical assays. The expression levels of angiotensin converting enzyme (ACE), Angiotensin II type 1 receptor (AT1R) and angiotensin converting enzyme 2 (ACE2) were examined by Western blotting. The expression levels of angiotensinII (AngII) and angiotensin-(1-7) (Ang-(1-7)) were measured through ELISA. MasR, IL-6, IL-1β and TNFα were all measured using qRT-PCR.. SND significantly ameliorated E. coli-induced ALI, including reducing inflammatory factors in lung tissue and the activity of MPO in serum. Furthermore, SND could obviously decrease the expression of ACE, AngII and AT1R, which were induced by E. coli. On the other hand, SND could markedly activate ACE2-Ang-(1-7)-Mas pathway.. In this paper, we demonstrated that SND alleviates E. coli induced acute lung injury in mice via equilibrating ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis.

Topics: Acute Lung Injury; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Drugs, Chinese Herbal; Escherichia coli; Escherichia coli Infections; Gene Expression Regulation; Male; Mice; Mice, Inbred ICR; Peptide Fragments; Peptidyl-Dipeptidase A; Proto-Oncogene Mas; Proto-Oncogene Proteins; Receptor, Angiotensin, Type 1; Receptors, G-Protein-Coupled; Renin-Angiotensin System

Shiga toxin 2 (Stx2)-producing enterohemorrhagic induced brain damage. Since a cerebroprotective action was reported for angiotensin (Ang)-(1-7), our aim was to investigate whether Ang-(1-7) protects from brain damage induced by Stx2-producing enterohemorrhagic Escherichia coli The anterior hypothalamic area of adult male Wistar rats was injected with saline solution or Stx2 or Stx2 plus Ang-(1-7) or Stx2 plus Ang-(1-7) plus A779. Rats received a single injection of Stx2 at the beginning of the experiment, and Ang-(1-7), A779, or saline was administered daily in a single injection for 8 days. Cellular ultrastructural changes were analyzed by transmission electron microscopy. Stx2 induced neurodegeneration, axonal demyelination, alterations in synapse, and oligodendrocyte and astrocyte damage, accompanied by edema. Ang-(1-7) prevented neuronal damage triggered by the toxin in 55.6 ± 9.5% of the neurons and the Stx2-induced synapse dysfunction was reversed. In addition, Ang-(1-7) blocked Stx2-induced demyelination in 92 ± 4% of the axons. Oligodendrocyte damage caused by Stx2 was prevented by Ang-(1-7) but astrocytes were only partially protected by the peptide (38 ± 5% of astrocytes were preserved). Ang-(1-7) treatment resulted in 50% reduction in the number of activated microglial cells induced by Stx2, suggesting an anti-inflammatory action. All these beneficial effects elicited by Ang-(1-7) were blocked by the Mas receptor antagonist and thus it was concluded that Ang-(1-7) protects mainly neurons and oligodendrocytes, and partially astrocytes, in the central nervous system through Mas receptor stimulation.

Topics: Angiotensin I; Animals; Escherichia coli Infections; Hypothalamus; Infectious Encephalitis; Male; Neuroprotective Agents; Peptide Fragments; Rats; Rats, Wistar; Shiga Toxin 2; Shiga-Toxigenic Escherichia coli; Treatment Outcome