The Effects of Dexmedetomidine in a Rat Model of Sepsis-Induced Lung Injury are Mediated Through the Adenosine Monophosphate-Activated Protein Kinase (AMPK)/Silent Information Regulator 1 (SIRT1) Pathway.

BACKGROUND This study aimed to investigate the effects of dexmedetomidine in a rat model of sepsis-induced lung injury and the role of the adenosine monophosphate-activated protein kinase (AMPK) gene and silent information regulator 1 (SIRT1) gene signaling pathway. MATERIAL AND METHODS Sixty 28-week-old healthy male Sprague-Dawley rats were randomly divided into three groups, the sham group, the model group, and the dexmedetomidine-treated group. The rat model of sepsis-induced lung injury was developed by surgical cecal ligation and puncture. Lung tissues examined histologically in the three study groups. Cell apoptosis was measured using the TUNEL assay, and the expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß (IL-1ß), and IL-10 were measured in rat lung tissue by enzyme-linked immunosorbent assay (ELISA). Apoptosis-associated proteins and AMPK/SIRT1 pathway-associated protein expression levels were detected using Western blot. RESULTS Dexmedetomidine significantly increased the survival rate and reduced the body temperature of rats in the model group with sepsis-induced lung injury, reduced lung injury, significantly reduced apoptosis in lung tissues, and reduced the expression levels of TNF-alpha, and IL-1ß, and increased the levels of IL-10. Dexmedetomidine significantly reduced the expression of caspase-3 in the rat lung tissue (P<0.01), and significantly increased the expression of Bcl-2/Bax and the phosphorylation levels of AMPK, SIRT1, nuclear factor-kappaB (NF-kappaB), and forkhead box class O 3a (FOXO3a). CONCLUSIONS In a rat model of sepsis-induced lung injury, dexmedetomidine reduced lung damage by activating the AMPK/SIRT1 signaling pathway and reduced the expression of inflammatory cytokines and cell apoptosis.

Hirudin, a thrombin inhibitor, attenuates TGF-ß-induced fibrosis in renal proximal tubular epithelial cells by inhibition of protease-activated receptor 1 expression via S1P/S1PR2/S1PR3 signaling.

Renal interstitial fibrosis (RIF) is the final common outcome of numerous chronic kidney diseases, contributing to end-stage renal disease. Hirudin, a thrombin inhibitor, has attracted increased attention as a potential treatment approach for renal fibrosis. The present study aimed to investigate the molecular mechanism underlying the effect of hirudin on fibrosis in renal proximal tubular epithelial cells. An in vivo mouse RIF model established using unilateral ureteral obstruction (UUO) and an in vitro of RIF using the renal tubular epithelial cell line HK-2 treated with TGF-ß were used. Expressions of sphingosine-1-phosphate (S1P) receptors (S1PR)1-4 and protease-activated receptor 1 (PAR1) were measured by reverse transcription-quantitative PCR and western blotting in mice with UUO and TGF-ß induced HK-2 cells. Western blotting was used to detect the expression of N-cadherin, Slug, E-cadherin, Collagen IV, fibronectin, MMP9 and monocyte chemoattractant protein-1. Immunofluorescence staining was conducted to measure α-SMA level expression. The results demonstrated that the expression levels of S1PR1, S1PR2, S1PR3, S1PR4 and PAR1 were upregulated in both TGF-ß-induced HK-2 cells and renal tissues from mice with unilateral ureteral ligation. Notably, hirudin inhibited TGF-ß-induced PAR1, S1PR2 and S1PR3 upregulation in both HK-2 cells and renal tissues. Additionally, the inhibition of S1PR2 and S1PR3 resulted in PAR1 downregulation. Furthermore, treatment with S1P and PAR1 agonists abolished the effect of hirudin on the expression of EMT, fibrosis-related proteins and monocyte chemoattractant protein 1. In conclusion, hirudin attenuated TGF-ß-induced fibrosis in proximal renal tubular epithelial HK-2 cells by inhibiting PAR1 expression via the S1P/S1PR2/S1PR3 signaling pathway. Therefore, hirudin may be considered as a promising therapeutic agent for RIF.

[Prevalence of sensitization to aeroallergens in 1 893 patients with allergic rhinitis in Yunnan].

OBJECTIVE: To investigate which aeroallergens were prevalent in patients with allergic rhinitis in Yunnan. METHOD: Retrospective analysis of the medical records of intradermal test performed in 1893 AR patients. The samples were divided into four age groups: 4-17-year-olds, > 17-35-year-olds, > 35-50-year-olds and > 50-70-year-olds. According to gender,the samples were decided into two groups: the males and the females. The positive rate of aeroallergens were compared among the groups. RESULT: (1)The total positive rate of intradermal test was 70.1%. The top ten allergens were as follow: dermatophagoides pteronyssinus, dermatophagoides farina, house dust, pollen of the summer and autumn, alnus nepalensis, chenopodiaceae, mugwort, poaceae, brassica and cockroach. (2) In all groups,patients with triple positive allergens were the most common,followed by dual positive allergens and single positive allergen. (3) Among the top ten allergens, the top three positive ones in all groups were dermatophagoides pteronyssinus, dermatophagoides farina and house dust. And there were significant differences between 4-17-year-olds group and the other age groups (P < 0.01). (4) There was no significant difference between male and female patients in distribution of aeroallergens except House dust and mite. CONCLUSION: The most common allergen in patients with allergic rhinitis in Yunnan is mite,the follow are pollen of the summer and autumn, alnus nepalensis, chenopodiaceae, mugwort, poaceae, and brassica. The distribution of aeroallergens are different among the age groups, but has no evident correlation with gender.