Protective effect of heme oxygenase-1 on Wistar rats with heart failure through the inhibition of inflammation and amelioration of intestinal microcirculation.
BACKGROUND
Myocardial infarction (MI) has likely contributed to the increased prevalence of heart failure (HF). As a result of reduced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 (HO-1) could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated.


METHODS
Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction of < 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI: saline; MI + Cobalt protoporphyrin (CoPP): CoPP solution; and MI + Tin mesoporphyrin IX dichloride (SnMP): SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiography was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bacterial translocation (BT) incidence, mesenteric microcirculation, amount of endotoxins in the vein serum, ileum levels of HO-1, carbon oxide (CO), nitric oxide (NO), interleukin (IL)-10, tumour necrosis factor-α (TNF-α), and the ileum morphology were determined eight weeks after the operation.


RESULTS
The rats receiving MI + CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-α levels, and an elevation in ileac HO-1, CO, and interleukin-10 (IL-10) levels compared to the MI group (P < 0.05). The rats that received the MI + SnMP injections exhibited results inverse to the MI (P < 0.05) group.


CONCLUSIONS
HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.
Department of Cardiology Internal Medicine, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Li
L
Zhang
VIP Cardiovascular Department, Navy General Hospital, Beijing, China.
Zhuo-Kun
ZK
Gan
Department of Cardiology Internal Medicine, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Li-Na
LN
Han
Department of Cardiology Internal Medicine, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Hao
H
Wang
Department of Clinical Laboratory, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Jie
J
Bai
Department of Ultrasonography, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Guo-Juan
GJ
Tan
Department of Clinical Laboratory, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Xiao-Xia
XX
Li
Department of Clinical Laboratory, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Ya-Ping
YP
Xu
Department of Clinical Laboratory, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Yu
Y
Zhou
Department of Clinical Laboratory, Nanlou Branch of Chinese PLA General Hospital, Beijing, China.
Mei-Liang
ML
Gong
School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, China.
Mo-Si
MS
Lin
Department of Pharmacy, Out-patient Clinic of Aerospace City, General Armament Hospital, Beijing, China.
Xiao-Yang
XY
Han
Carbon monoxide; Heart failure; Heme oxygenase-1; Intestine