الملخص
Objective To observe the effect of Shenfu injection on lung injury caused by hemor-rhagic shock(HS)in rats and explore the related potential mechanism.Methods Thirty-six SPF healthy male SD rats,aged 16-17 weeks,weighing 400-600 g,were randomly divided into three groups:sham op-eration group(group SH),HS group(group HS),and Shenfu injection group(group SF),12 rats in each group.In group SH,only the right femoral vein and femoral artery were separated after anesthesia,and ve-nous catheterization was not performed.HS model was established in groups SF and HS.In group HS,liquid resuscitation was performed through an intravenous catheter,and the resuscitation fluid consisted of the auto-blood lost and the compound sodium chloride injection equivalent to 1.5 times the blood loss and 10 ml/kg normal saline.In group SF,the resuscitation fluid consisted of the lost autoblood and the compound sodium chloride injection equivalent to 1.5 times the blood loss and Shenfu injection 10 ml/kg.The whole perfusion time was about 60 minutes.Six rats in the three groups were randomly anesthetized 24 and 48 hours after op-eration.The wet/dry weight ratio(W/D)of lung tissues was detected.The concentrations of interleukin-6(IL-6),IL-17,IL-10,and transforming growth factor-β(TGF-β)were detected by ELISA,the mRNA ex-pression of retinoic acid-related orphan nuclear receptor γt(RORγt),transcription factor forkhead box pro-tein 3(Foxp3),and hypoxia-inducible factor-1α(HIF-1α)in lung tissues were detected by PCR.The pro-tein contents of RORγt,Foxp3,HIF-1α,aquaporin 1(AQP1),and AQP5 in lung tissue were detected by Western blot.Pathological changesunder HE staining light microscope and lung injury scores were observed.Results Compared with 24 hours after operation,W/D,the concentrations of IL-6 and IL-17,mRNA ex-pression and protein content of RORγt and HIF-1α,and lung injury score were significantly decreased(P＜0.05),the concentrations of IL-10,and TGF-β,Foxp3 mRNA expression and protein content,and AQP1 protein content were significantly increased in group SF 48 hours after operation(P＜0.05).Compared with group SH,W/D,the concentrations of IL-6,IL-17,IL-10,and TGF-β,mRNA expression and protein content of RORγt,Foxp 3,and HIF-1α,and lung injury score were significantly increased(P＜0.05),AQP1 and AQP5 protein contents were significantly decreased in groups HS and SF 24 and 48 hours after operation(P＜0.05),and alveolar structure was damaged under light microscope and alveolar interstitium was filled with a large amount of edematous fluid,during which a large number of inflammatory cells infiltra-ted.Compared with group HS,W/D,the concentrations of IL-6 and IL-17,mRNA expression and protein content of RORγt and HIF-1α,and lung injury score were significantly decreased(P＜0.05),the concen-trations of IL-10 and TGF-β,Foxp3 mRNA expression and protein content,AQP1 and AQP5 protein con-tents were significantly increased in group SF 24 and 48 hours after surgery(P＜0.05),and the alveolar structure was improved under light microscope,and edema was reduced,and the number of inflammatory cells was reduced.Conclusion Shenfu injection can regulate the balance between pro-inflammatory factors IL-6 and IL-17,and anti-inflammatory factors IL-10 and TGF-β,increase the protein content of AQP1 and AQP5 in lung tissue,and decrease the W/D and injury score in lung tissue,thus alleviating lung injury in HS rats.The mechanism may be related to the regulation of HIF-1α-RORγt/Foxp3 balance.
الملخص
Objective:To investigate the change in 25-hydroxy vitamin D (25-OHD) levels in hospitalized newborns in the neonatal intensive care unit (NICU) between baseline and vitamin D supplementation, and to explore the effect of different levels of vitamin D on the complications.Method:A prospective study was conducted on the newborns admitted to NICU at Jingzhou Hospital Affiliated to Yangtze University within 72 h after birth from January 2021 to January 2022. Vitamin D supplementation was initiated after the detection of basal 25-OHD levels within 72 h after birth. Serum 25-OHD levels were measured after 2, 4, and 6 weeks of supplementation. Newborns were categorized into four groups according to the basal 25-OHD level: sufficient, insufficient, deficient, and severely deficient groups. The analysis of variants, independent sample t-test, paired sample t-test, Chi-square test, or Fisher's exact probability method were employed to evaluate the differences in basal 25-OHD levels among newborns with different clinical conditions and gestational ages, as well as the variation in 25-OHD levels before and after supplementation among the four groups. Furthermore, differences in the morbidity and mortality among different basal status groups were analyzed. Result:(1) During the study period, 626 cases met the inclusion criteria, and after excluding seven cases, 619 infants were ultimately included in the study with serum 25-OHD level within 72 h being (21.8±10.1) ng/ml. There were 134 cases (21.6%) in the sufficient group, 208 cases (33.6%) in the insufficient group, 186 cases (30.0%) in the deficient group, and 91 cases (14.7%) in the severe deficient group. (2) No statistically significant differences were observed in the basal 25-OHD levels regardless of the genders, gestational age, birth month, number of fetuses or small for gestational age (all P>0.05). (3) Among all infants, 158 cases continued to supplement vitamin D for two weeks, 64 cases continued for four weeks, and 13 cases continued for six weeks, with all of them discharged within eight weeks. Compared with the basal 25-OHD levels, there were no statistically significant differences in the serum 25-OHD levels among the sufficient, insufficient, deficient, and severely deficient groups after two weeks of supplementation [(37.1±9.3) vs. (36.8±4.9) ng/ml, (24.7±7.2) vs. (24.7±2.9) ng/ml, (16.0±7.6) vs. (15.4±2.9) ng/ml, (8.1±5.6) vs. (7.6±1.4) ng/ml; t=0.18, 0.04, 0.65 and 0.48, respectively; all P>0.05]. After four weeks of supplementation, however, the serum 25-OHD levels in the four groups were higher than those before supplementation [(40.0±5.2) vs. (35.8±3.9) ng/ml, (29.7±6.4) vs. (24.5±2.9) ng/ml, (20.3±7.1) vs. (15.6±3.0) ng/ml, (14.9±7.3) vs. (6.5±2.3) ng/ml; t=2.13, 2.66, 5.08 and 7.64, respectively; all P<0.05]. (4) The incidence of hypocalcemia [23.1% (21/91) vs. 9.7% (18/186)] and neonatal respiratory distress syndrome [15.4% (14/91) vs. 3.2% (6/186)] were higher in the severely deficient group than those in the deficient group ( χ2=9.07 and 13.49, both P<0.008). No statistically significant differences were observed in the incidence of neonatal sepsis, neonatal necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, and mortality among the four groups (all P>0.05). Conclusions:The insufficiency of 25-OHD levels and vitamin D deficiency were prevalent in NICU neonates. Vitamin D status did not significantly differ among newborns with varying gestational ages. A prolonged period of sustained vitamin D supplementation may be required to elevate the serum 25-OHD level. The incidence of hypocalcemia and neonatal respiratory distress syndrome are higher in newborns with severe vitamin D deficiency.