Effect of penehyclidine hydrochloride on the expression of Toll-like receptor 4 during acute lung injury / 中华急诊医学杂志

ABSTRACT

Objective To observe the effects of penehydidine hydrochloride (PHC) on t acute lung injury ( ALI) . To investigate into the expression of TLR4 on peripheral monocytes, kinetics of inflammatory and anti- inflammatory mediators. To explore the mechanism of TLR4 in ALI. Method A total of 45 patients with ALI were randomly divided into PHC treatment group(experimental group, n =21) and routine treatment group (control group, n = 24) . Patients of both groups were given with the routine treatment,and patients in experimental group were given with PHC in addition (1 mg,im,ql2h) . Therapeutic effects, average length of hospital stay, ICU stay,PaO_2 and PaO_2/FiO_2 > as well as the expression of TLR4 and some cytokines were observed for 48 hours. Results Patients of both groups got better gradually after treatment. The PaO_2 and PaO_2/FiO_2 of patients of both groups progressively increased. At 6 hours, 12 hours, 24 hours and 48 hours after treatment, the PaO_2 and PaO_2/FiO_2significantly increased than 0 hour ( P < 0.05). The improvement in experimental group was obviously better than that in control group at 6 hours, 24 hours and 48 hours after treatment (P < 0.05). There were no differences in average length of hospital stay between the two groups. The ICU stay was significantly shorter in the experimental group ( P < 0.01) . The expressions of TLR4 were higher in patients of both groups than in healthy ones (P <0.01) . TLR4 decreased significantly at 24 hours and 48 hours, while it was lower in experimental group than that in the control group (P < 0.05). The higher level of TLR4in the early stage implied worse prognosis. Most of them deteriorated to ARDS stage. At 24 hours, the incidence of ARDS in experimental group was 23.8 % , and 29.17% in control group. Two patients in control group didn' t become ARDS till 48 hours. Serum IL-1, IL-8 and TNF-α level reduced atr 24 hours in both groups. The reduction of IL-8 and TNF-α in experimental group was more obvious than in control group ( P < 0.05). IL-13 increased gradually from 0 hour to 24 hours, then descended a little at 48 hours. There was no difference in IL-13 some difference between the two groups ( P > 0.05) . Conclusions PHC can improve the arterial oxygen pressure, down-regulate TLR4, restrain inflammatory factors in its signal transduction downstream. This inhibitory action is not accomplished by increase in anti-inflammatory factors,but by down-regulating TLR4. PHC can prevent the development of ALI, and can be considered to act as an effective medicine for the treatment of ALI. TLR4 plays an important role in ALT process, and it is suggested that TLR4 can be used as a prognostic factor.