Interleukin-6 contributes to myocardial damage in pregnant rats with reduced uterine perfusion pressure

Abstract

Preeclampsia is one of the most frequent and difficult illnesses in pregnancy, which jeopardizes both mother and fetus. There are several diagnostic criteria for preeclampsia. However, the preeclampsia-associated myocardial damage has not been described. In this study, we employed reduced uterine perfusion pressure (RUPP) to generate a rat model of preeclampsia for the evaluation of myocardial damage in late-gestation rats. The expressions of cardiac injury markers were analyzed by immunohistochemistry and ELISA. The arterial pressure and myocardial tissue velocities were also measured. The role of interleukin (IL)-6 in RUPP-associated myocardial damage was further explored. The results showed that RUPP rats had significant myocardial damage, as demonstrated by the high expressions of myoglobin, creatine kinase isoenzyme, cardiac troponin I, and brain natriuretic peptide. In addition, RUPP increased the mean arterial pressure and the early transmitral flow velocity to mitral annulus early diastolic velocity ratio (E/Ea). Furthermore, IL-6 deteriorated these abnormalities, whereas inhibition of IL-6 significantly relieved them. In conclusion, our study demonstrated that RUPP rats displayed myocardial damage in an IL-6-dependent manner.

Figure 1.. Rats were subjected to reduced uterine perfusion pressure (RUPP) or sham operation and then intraperitoneally injected with interleukin (IL)-6 (50 ng/day) for 5 days. A, Expression of IL-6 in cardiac tissue was assayed by immunohistochemistry. Scale bar: 100 μm. B, Expression of IL-6 in serum was measured by ELISA. Experiments were repeated at least three times (n=6). Data are reported as means±SD. *P<0.05 vs control, ^#P<0.05 vs RUPP (one-way ANOVA).

Figure 2.. Rats were subjected to reduced uterine perfusion pressure (RUPP) or sham operation and then intraperitoneally injected with interleukin (IL)-6 (50 ng/day) for 5 days. A-C, Concentrations of cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and myoglobin (Mb) in serum were detected by ELISA. D and E, Expressions of brain natriuretic peptide (BNP) in cardiac tissue and serum were detected by immunohistochemistry and ELISA. Scale bar: 100 μm. Experiments were repeated at least three times (n=6). Data are reported as means±SD. *P<0.05 vs control, ^#P<0.05 vs RUPP (one-way ANOVA).

Figure 3.. Rats were subjected to reduced uterine perfusion pressure (RUPP) or sham operation and then intraperitoneally injected with interleukin (IL)-6 (50 ng/day) for 5 days. A, Arterial pressure was monitored with a pressure transducer connected to an arterial pressure-recording device. B-D, Myocardial systolic peak velocity (Sm), early diastolic velocity (Ea), and late diastolic velocity (Aa) in three cardiac cycles were measured using tissue Doppler echocardiography. E, Early diastolic/late diastolic velocities ratio (E/Ea). All experiments were repeated at least three times (n=6). Data are reported as means±SD. *P<0.05 vs control, ^#P<0.05 vs RUPP (one-way ANOVA).

Figure 4.. Rats were subjected to reduced uterine perfusion pressure (RUPP) or sham operation and then intraperitoneally injected with interleukin (IL)-6 (50 ng/day) and tocilizumab (8 mg/kg) for 5 days. A, Expression of IL-6 in cardiac tissue was assayed by immunohistochemistry. Scale bar: 100 μm. B-D, Expression of IL-6, brain natriuretic peptide (BNP), and creatine kinase isoenzyme (CK-MB) in serum was measured by ELISA. E, Early diastolic/late diastolic velocities ratio (E/Ea). All experiments were repeated at least three times (n=6). Data are reported as means±SD. *P<0.05 vs control, ^#P<0.05 vs RUPP (one-way ANOVA).