Effect of penehyclidine hydrochloride on patients with acute lung injury and its mechanisms.
OBJECTIVE
To assess the effects of penehyclidine hydrochloride on patients with acute lung injury (ALI), to observe the expression of Toll-like receptor 4 (TLR4) on the peripheral monocytes of ALI patients and changes of inflammatory and anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI.


METHODS
Forty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group (P group, n equal to 21) and conventional treatment group (control group, C group, n equal to 24). Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride (1 mg, im, q. 12 h) in addition. The TLR4 expression of 20 healthy volunteers were detected. The clinical effect, average length of stay in ICU and hospital, values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h.


RESULTS
The general conditions of the two groups were improved gradually and PaO2 increased progressively. Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased (P less than 0.05). The improvement in P group was obviously greater than that in C group (P less than 0.05). The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU (t equal to 3.485, P less than 0.01). The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers (P less than 0.01). It decreased significantly at 24 h (t equal to 2.032, P less than 0.05) and 48 h (t equal to 3.620, P less than 0.01) and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome (ARDS). The incidence of ARDS was 23.8% in P group and 29.17% in C group at 24 h. Untill 48 h, there were other two patients developing ARDS in control group. Serum IL-1, IL-8 and TNF-alpha expressions reduced after 24 h in both groups. The reduction in P group was more obvious than that in C group (P less than 0.05). IL-13 increased gradually from 0 h to 24 h, and decreased slightly at 48 h, which showed no difference between two groups (t equal to 1.028, P larger than 0.05).


CONCLUSIONS
Penehyclidine hydrochloride improves the arterial oxygen pressure, down-regulates the expression of TLR4 and restrains the inflammatory cytokines in the downstream of TLR4 signaling pathway. It prevents the development of ALI and can be considered as an important drug in ALI treatment.
Department of Emergency Medicine, Nanjing General Hospital of Nanjing Military Command, School of Medicine, Nanjing University, Nanjing 210002, China.
Bai-qiang
BQ
Li
Hai-chen
HC
Sun
Shi-nan
SN
Nie
Dan-bing
DB
Shao
Hong-mei
HM
Liu
Xiao-ming
XM
Qian
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016207:Cytokines / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D010100:Oxygen / Q000097:blood; D011379:Prognosis; D011812:Quinuclidines / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology
D016207:Cytokines; D011812:Quinuclidines; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C486140:penehyclidine; D010100:Oxygen