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. 2015 Jul;12(4):353-65.
doi: 10.11909/j.issn.1671-5411.2015.04.001.

Protective Effect of Heme oxygenase-1 on Wistar Rats With Heart Failure Through the Inhibition of Inflammation and Amelioration of Intestinal Microcirculation

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Protective Effect of Heme oxygenase-1 on Wistar Rats With Heart Failure Through the Inhibition of Inflammation and Amelioration of Intestinal Microcirculation

Li Zhang et al. J Geriatr Cardiol. .
Free PMC article

Abstract

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.

Keywords: Carbon monoxide; Heart failure; Heme oxygenase-1; Intestine.

Figures

Figure 1.
Figure 1.. LvEF% of rats at baseline (A, n = 8) and eight weeks postoperative (B, n = 8), and rats for microcirculation test (C, n = 4).
*P < 0.05, **P < 0.01vs. Control; #P < 0.05, ##P < 0.01 vs. MI. CoPP: cobalt protoporphyrin; LvEF: left ventricular ejection fraction; MI: myocardial infarction; SnMP: Tin mesoporphyrin IX dichloride.
Figure 2.
Figure 2.. Endotoxin levels of plasma in both portal vein (A) and inferior vena cava (B) eight weeks postoperative.
N = 10 in each group. *P < 0.05, **P < 0.01 compared to the Control group; #P < 0.05, ##P < 0.01 compared to the MI group. CoPP: cobalt protoporphyrin; LvEF: left ventricular ejection fraction; MI: myocardial infarction; SnMP: Tin mesoporphyrin IX dichloride.
Figure 3.
Figure 3.. HO-1 expression level in ileum determined by Real-time PCR (A) and Western blotting (B&C), and CO level (D).
*P < 0.05, **P < 0.01 compared to the Control group; #P < 0.05, ##P < 0.01 compared to the MI group. CO: carbon oxide; CoPP: cobalt protoporphyrin; HO-1: heme oxygenase-1; MI: myocardial infarction; SnMP: Tin mesoporphyrin IX dichloride.
Figure 4.
Figure 4.. Ileac NO level.
*P < 0.05, **P < 0.01 compared to the Control group; #P < 0.05, ##P < 0.01 compared to the MI group. Copp: cobalt protoporphyrin; MI: myocardial infarction; NO: nitric oxide; SnMP: Tin mesoporphyrin IX dichloride
Figure 5.
Figure 5.. Ileac TNF-α and IL-10 expression levels determined by real-time PCR (A & C, n = 5) or ELISA (B & D, n = 8).
*P < 0.05, **P < 0.01 compared to the Control group; #P < 0.05, ##P < 0.01 compared to the MI group. CoPP: cobalt protoporphyrin; IL-10: interleukin-10; MI: myocardial infarction; TNF: tumor necrosis factor; SnMP: Tin mesoporphyrin IX dichloride.
Figure 6.
Figure 6.. Determination of mesenteric microcirculation (n = 4).
(A): Number of Adherent Leukocytes in grade III stretching venule (V3) of per millimeter vessel within a period of 60 s; (B): Diameter of grade III stretching Arteriole; (C): capillary diameter; and (D): Perfusion of villi. *P < 0.05, **P < 0.01 compared to the Control group; #P < 0.05, ##P < 0.01 compared to the MI group. CoPP: cobalt protoporphyrin; MI: myocardial infarction; SnMP: Tin mesoporphyrin IX dichloride.
Figure 7.
Figure 7.. Score of morphological examination of ileum.
*P < 0.05, **P < 0.01 compared to the Control group; #P < 0.05, ##P < 0.01 compared to the MI group. CoPP: cobalt protoporphyrin; MI: myocardial infarction; SnMP: Tin mesoporphyrin IX dichloride.
Figure 8.
Figure 8.. Morphological examination of ileum.
(A): Control, The normal morphology of the ileum; (B): MI + CoPP, CoPP protected the ileum from ischemia, and only mild edema was observed; (C): MI, The necrosis at the villus tip; (D): MI + SnMP, SnMP aggravated the necrosis. CoPP: cobalt protoporphyrin; MI: myocardial infarction; SnMP: Tin mesoporphyrin IX dichloride.

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