ABSTRACT
Shenfu Injection(SFI) is praised for the high efficacy in the treatment of septic shock. However, the precise role of SFI in the treatment of sepsis-associated lung injury is not fully understood. This study investigated the protective effect of SFI on sepsis-associated lung injury by a clinical trial and an animal experiment focusing on the hypoxia-inducing factor-1α(HIF-1α)-mediated mitochondrial autophagy. For the clinical trial, 70 patients with sepsis-associated lung injury treated in the emergency intensive care unit of the First Affiliated Hospital of Zhengzhou University were included. The levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α were measured on days 1 and 5 for every patient. Real-time quantitative polymerase chain reaction(RT-qPCR) was performed to determine the mRNA level of hypoxia inducible factor-1α(HIF-1α) in the peripheral blood mononuclear cells(PBMCs). For the animal experiment, 32 SPF-grade male C57BL/6J mice(5-6 weeks old) were randomized into 4 groups: sham group(n=6), SFI+sham group(n=10), SFI+cecal ligation and puncture(CLP) group(n=10), and CLP group(n=6). The body weight, body temperature, wet/dry weight(W/D) ratio of the lung tissue, and the pathological injury score of the lung tissue were recorded for each mouse. RT-qPCR and Western blot were conducted to determine the expression of HIF-1α, mitochondrial DNA(mt-DNA), and autophagy-related proteins in the lung tissue. The results of the clinical trial revealed that the SFI group had lowered levels of inflammatory markers in the blood and alveolar lavage fluid and elevated level of HIF-1α in the PBMCs. The mice in the SFI group showed recovered body temperature and body weight. lowered TNF-α level in the serum, and decreased W/D ratio of the lung tissue. SFI reduced the inflammatory exudation and improved the alveolar integrity in the lung tissue. Moreover, SFI down-regulated the mtDNA expression and up-regulated the protein levels of mitochondrial transcription factor A(mt-TFA), cytochrome c oxidase Ⅳ(COXⅣ), HIF-1α, and autophagy-related proteins in the lung tissue of the model mice. The findings confirmed that SFI could promote mitophagy to improve mitochondrial function by regulating the expression of HIF-1α.
Subject(s)
Humans , Male , Mice , Animals , Leukocytes, Mononuclear , Mice, Inbred C57BL , Lung/metabolism , Acute Lung Injury/drug therapy , Tumor Necrosis Factor-alpha/genetics , Sepsis/genetics , Hypoxia/pathology , Autophagy-Related Proteins , Body Weight , Drugs, Chinese HerbalABSTRACT
PURPOSE: To investigate the prevalence of spina bifida occulta (SBO) and its relationship with the presence of overactive bladder (OAB) in middle-aged and elderly people in China. METHODS: A cross-sectional community-based survey was carried out at 7 communities in Zhengzhou City, China from December 15, 2013 to June 10, 2014, where residents aged over 40 years were randomly selected to participate. All of the participants underwent lumbosacral radiographic analysis and relevant laboratory tests. A questionnaire including basic information, past medical history and present illness, and the OAB symptom score was filled out by all participants. Chi-square tests and logistic regression were used for data analysis with a P-value of 0.05). In men, age, SBO, and constipation were risk factors for OAB (P0.05). In women, age, SBO, and HCI were risk factors for OAB (P0.05). CONCLUSIONS: The prevalence of SBO is high and it is related to OAB in middle-aged and elderly people in China.