ABSTRACT
OBJECTIVE: To explore the mechanism of bone marrow mesenchymal stem cells(BMSCs) in alleviating silica-induced lung injury in mice. METHODS: Ten specific pathogen free healthy male C57 BL/6 mice were selected for isolating BMSCs and bone marrow macrophages(BMDMs). Transwell chamber was used, BMDMs were inoculated onto the upper chamber and BMSCs in the lower chamber. We divided them into sequencing control group and silica(SiO_2) exposure group. All cells were pre-stimulated with 50 μg/L mass concentration lipopolysaccharide for 4 hours. In the SiO_(2 ) group, 250 mg/L mass concentration SiO_2 was added to the upper chamber of transwell and cultured for 16 hours. Total RNA was extracted from the BMSCs collected from the lower chamber. HiSeq/MiSeq high-throughput sequencing technology was used to detect the BMSCs RNA paired-end sequencing. Transcriptome sequencing data was obtained and bioinformatics analysis was performed. Another 12 specific pathogen free healthy male C57 BL/6 mice were randomly divided into control group and experimental group. All mice received one intra-tracheal injection of 20.0 μL(250 g/L mass concentration) of silica dust suspension. After 6 hours, the mice in the control group was given 500.0 μL of 0.9% sodium chloride solution and mice in the experimental group was given 500.0 μL of BMSCs suspension(cell density 1×10~9/L) by tail vein infusion.Mice were sacrificed 12 hours later. The relative mRNA expression of interleukin(IL)-1 Ra, IL-10, tumor necrosis factor stimulating gene 6(TSG-6) and prostaglandin E2(PGE2) in lung tissues of mice were measured by quantitative real-time PCR(q-PCR). Meanwhile, BMDMs and BMSCs transwell co-culture models were established. The cells were divided into 5 groups: BMSCs group, BMSCs+BMDMs group, BMSCs+BMDMs+ lipopolysaccharide(LPS) group, 50 mg/L SiO_2 group, and 100 mg/L SiO_2 group. After 16 hours of corresponding SiO_2 stimulation, BMSCs of each group were collected and the relative mRNA expression levels of IL-1 Ra, IL-10, TSG-6, and PGE2 in the cells were detected by q-PCR. RESULTS: Compared with sequencing control group, BMSCs co-cultured with SiO_2 had 19 genes up-regulated and 21 genes down-regulated, including 10 genes up-regulated for more than 2.0-fold. The relative mRNA expression of IL-1 Ra, IL-10, PGE2 and TSG-6 in the lung tissue of mice increased in the experimental group than that of the control group(all P<0.05). The relative mRNA expression of TSG-6 increased by 37.5 times higher than that of the control group. Compared with the BMSCs+BMDM+LPS group, the level of TSG-6 mRNA relative expression increased in both the 50 mg/L SiO_2 group and the 100 mg/L SiO_2 group(all P<0.05). CONCLUSION: TSG-6 could be the key factor of BMSCs that can attenuate silica-induced lung injury.
ABSTRACT
Mesenchymal stem cells(MSCs) have functions such as immune regulation and tissue damage repair, but the specific mechanisms of their effects need to be further studied. Paracrine effect is an important mechanism for MSCs to achieve immune regulation, relieve inflammation and repair tissue damage. Tumor necrosis factor α(TNF-α) stimulated protein 6(TSG-6) is one of the paracrine factors of MSCs, which has significant inflammation inhibitory capability and tissue repair ability. It is an important cytokine of MSCs to exert their anti-inflammatory and anti-fibrotic effects. The MSCs can repair tissue damage in kidney, peritonea, skin, liver, lung, cornea, nervous system, and colon by secreting TSG-6. This powerful repair ability could be attributed to the ability of TSG-6 to inhibit the secretion of pro-inflammatory cytokines and pro-fibrogenic factors, such as TNF-α, interleukin(IL)-6, IL-1β and transforming growth factor-β1, thereby reducing the inflammatory response and fibrosis of the body.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the clinical effect and efficacy of Xiaozhi Capsule (XZC), a Chinese medicine preparation for tonifying Gan-Shen, invigorating Pi to dissipate dampness (TGSIPDD) on total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and endothelin (ET) in treating patients with hyperlipidemia.</p><p><b>METHODS</b>Totally 120 primary hyperlipidemia patients were randomly assigned to the treatment group (80 cases) and the control group (40 cases). Those in the treatment group took XZC, while those in the control group took Xuezhikang Capsule (XZKC). The serum TC, TG, HDL-C, LDL-C, and ET were detected and evaluated after 8 weeks of treatment.</p><p><b>RESULTS</b>In the treatment group TC was reduced by 25.60%, TG by 33.70%, LDL-C by 32.90%, and ET by 11.02%, while HDL-C was elevated by 24.20%. In the control group, TC was reduced by 24.80%, TG by 33.50%, LDL-C by 31.30%, and ET by 12.05%, while HDL-C was elevated by 20.90%. There was statistical difference in the two groups when compared with before treatment (P < 0.01). But there was no statistical difference in the aforesaid indices between the two groups after treatment (P > 0.05). The integrals for main symptoms after treatment obviously decreased in the two groups, showing statistical difference when compared with before treatment in the same group (P < 0.01). But there was no statistical difference in the aforesaid indices between the two groups (P > 0.05). After 8 weeks of treatment, symptoms such as vertigo, heavy sensation of head, palpitation, chest distress, dry mouth and thirsty were obviously improved after treatment. There was statistical difference in the improvement of tinnitus after treatment in the treatment group (P < 0.01). The total effective rate was 86.25% in the treatment group and 82.50% in the control group, showing no statistical difference (P > 0.05).</p><p><b>CONCLUSIONS</b>XZC showed certain effects on each blood lipid index and ET of hyperlipidemia patients. It had better improvement of clinical symptoms with reliable efficacy.</p>