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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (2): 240-245. doi: 10.19723/j.issn.1671-167X.2021.02.002

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Effects of ultrafine particulates on cardiac function in rat isolated heart

BAI Feng,HE Yi-fan,NIU Ya-nan,YANG Ruo-juan,CAO Jing()   

  1. Department of Cardiology, The First Hospital of Shanxi Medical University & Department of Pharmacology, Basic Medical School, Shanxi Medical University, Taiyuan 030001, China
  • Received:2019-07-17 Online:2021-04-18 Published:2021-04-21
  • Contact: Jing CAO E-mail:13834691242@163.com
  • Supported by:
    International Cooperation Project of Shanxi(2012081046)

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Abstract:

Objective: To evaluate whether ultrafine particulates (UFPs) have direct deleterious effects on cardiac function through activating MAPK signaling. Methods: Langendorff-perfused Sprague-Dawley rat hearts were randomly divided into 2 groups (n=10/each group). In control group, the rat hearts were perfused with Tyrode’s buffer for 40 min; in UFPs-treated group, the hearts were perfused with UFPs at a concentration of 12.5 mg/L. Cardiac function was determined by measuring left ventricular developed pressure (LVDP), left ventricular peak rate of contraction and relaxation (±dp/dtmax) and coronary flow (CF). The levels of malondialdehyde (MDA), superoxide dismutase (SOD), total anti-oxidant capacity (TAOC) were detected in order to evaluate cardiac oxidative stress via the thiobarbituric acid assay, water soluble tetrazolium salt assay and colorimetry, respectively. The expressions of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium were observed using immunohistochemical staining and Western blots. Results: No significant changes in cardiac function were detected before and after the perfusion in control group while UFPs perfused hearts showed a decline in cardiac function in a time-dependent manner (all P<0.05). In UFPs-treated group, LVDP, +dp/dtmax, -dp/dtmax and CF were statistically reduced from (82.6±2.1) mmHg, (1 624±113) mmHg/s, (1 565±116) mmHg/s, (12.0±0.2) mL/min to (56.8±4.4) mmHg, (1 066±177) mmHg/s, (1 082±134) mmHg/s, (8.7±0.3) mL/min (all P<0.05), respectively. Furthermore, The comparison between the two groups observed that UFPs perfusion caused a significant decrease in cardiac function at 30 and 40 min compared with the control group (all P<0.05). At the end of the perfusion, the level of MDA was increased from (0.98±0.14) nmol/L to (1.95±0.18) nmol/L, while SOD and TAOC were reduced from (12.50±1.87) U/mL and (6.83±1.16) U/mL to (6.50 ±1.04) U/mL and (3.67±0.82) U/mL (all P<0.001) in UFPs group, respectively. In coincidence with these changes, immunohistochemistry and Western blots results showed that the levels of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium significantly increased in UFPs group as compared with control group (all P<0.05). Conclusion: The results of this study demonstrated that the short-term exposure of UFPs to the isolated rat hearts has direct and acute toxic effects on cardiac function, probably related to attenuation of anti-oxidative capacity and activation of MAPK signaling pathways.

Key words: Ultrafine particulates(UFPs), Isolated rat heart, Oxidative stress, MAPK

CLC Number: 

  • R122.7

Figure 1

Effect of UFPs (12.5 mg/L) perfusion on isolated rat heart n=10、 A, LVDP; B, +dp/dtmax; C,-dp/dtmax; D, CF. *P<0.05 vs. UFPs-treated group at 0 min, # P<0.05 vs. control group at the same time point."

Table 1

The comparison of MDA, TAC and SOD in the outflow of pulmonary artery between the two groups ($\bar{x} \pm s$)"

Group n MDA/(nmol/L) SOD/(U/mL) TAOC/(U/mL)
Control 10 0.98±0.14 12.5±1.87 6.83±1.16
UFPs 10 1.95±0.18 6.50±1.04 3.67±0.823
t 29 10.39 6.63
P <0.001 <0.001 0.001

Figure 2

UFPs intervention caused deterioration of cardiac function A and B, control group perfusion map and perfusion trend graph; E and F, UFPs group perfusion map and perfusion trend graph. C and G, control group and UFPs group perfusion end heart. D and H, the pathological changes of myocardium in control group and UFPs group (HE staining ×400)."

Figure 3

Pathological changes of rat myocardium (IHC ×400) Immunohistochemical images showed the expression of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium of normal control group and UFPs-treated group (×400). The UFPs treatment group showed high expression of p-p38 MAPK, p-ERKs and p-JNKs (indicated by arrows)."

Figure 4

UFPs perfused for 30 minutes, induced the phosphorylation of MAPK family members The levels of phosphorylated p38 MAPK, ERKs and JNKs were determined by Western blots assay. Values are given as $\bar{x} \pm s$, n=6 for each group. *P<0.05, UFPs-treated group vs. normal control group. "

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