Effects of Chaihu-Shugan decoction on ROCK/JNK signaling pathway and atherosclerosis in spontaneously hypertensive rats

AIM To observe the effect of Chaihu-Shugan decoction (CHSGD) on atherosclerosis in spontaneously hypertensive rats (SHR) and its possible mechanism. METHODS The male SHR (n=50) were randomly divided into model group (gavage of normal saline), compound kendir leaves (CKL) group (gavage of 0.5 g/kg CKL), and low-, medium- and high-dose CHSGD (CHSGD-L, CHSGD-M and CHSGD-H) groups (gavage of 2.5, 5 and 10 g/kg CHSGD, respectively), and another 10 male Wistar rats of the same origin were selected as normal control （NC) group (gavage of normal saline). The blood pressure was measured by intelligent noninvasive sphygmomanometer. The levels of blood lipids were measured by automatic biochemical analyzer. The expression of oxidative stress-related indexes, nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD), were detected by colorimetry. HE staining was used to detect the degree of atherosclerosis, and Western blot was used to detect the expression of Rho-associated kinase (ROCK)/c-Jun N-terminal kinase (JNK) signaling pathway-related proteins, RhoA, ROCK1 and JNK. RESULTS After 4 weeks of treatment, compared with NC group, the blood pressure, the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and MDA, and the protein expression of RhoA, ROCK1 and JNK in aortic tissues of the rats in model group were significantly increased (P<0.05), and the serum levels of high-density lipoprotein cholesterol, NO and SOD were significantly decreased (P<0.05). HE staining showed that the diameter of aortas in the rats was thickened, a large number of foam cells were formed under the endothelium, and the proliferation of smooth muscle cells was observed. Compared with model group, the blood pressure, the serum levels of TG, TC, LDL-C and MDA, and the protein expression of RhoA, ROCK1 and JNK in aortic tissues of the rats in CKL, CHSGD-L, CHSGD-M and CHSGD-H groups were significantly decreased (P<0.05), and the serum levels of NO and SOD were significantly increased (P<0.05). HE staining showed that the structure of each layer of rat aortas gradually returned to normal, the vascular cells were in good order, and the inflammatory cell infiltration was slight. Compared with CKL group, the blood pressure, the serum levels of TG, TC, LDL-C and MDA, and the protein expression of RhoA, ROCK1 and JNK in aortic tissues of the rats in CHSGD-L and CHSGD-M groups were significantly increased (P<0.05), and the serum levels of NO and SOD were significantly decreased (P<0.05). No significant difference of the above indexes between CHSGD-H group and CKL group was observed (P>0.05). CONCLUSION Chaihu-Shugan decoction may attenuate the oxidative stress response via inhibition of ROCK/JNK signaling pathway, thus alleviating the symptoms of atherosclerosis in SHR.