ESTABLISHMENT OF ERECTILE DYSFUNCTION (ED) RAT MODEL WITH COLD COAGULATION AND PHLEGMATIC BLOOD STASIS SYNDROME AND THE MODULATING EFFECT OF YIMUSAKE TABLETS

Abstract

Background: Researchers have recently focused a lot of attention on erectile dysfunction (ED), a major concern for males. Chinese medicine can be used for the diagnosis and prevention of ED. According to Chinese medicine, ED is primarily caused by blood stasis. Animal models based on etiological modeling are lacking. Yimusake tablet is a traditional Chinese medicine that is administered for treating various types of ED; however, studies on its effects on ED with blood stasis are lacking. Objectives: To investigate the characteristics of sexual function, penile histology, and the impact of Yimusake tablets, a rat model of cold coagulation and phlegmatic blood stasis syndrome (CCPTBS) was developed. Our study might act as a framework and lay the foundation for future basic and drug-focused research. Methods: To establish the CCPTBS rat model, the rats were exposed to long-term low-temperature conditions and administered a high-fat diet. Rats with ED were identified and treated with Yimusake tablets. The effectiveness of the treatment was determined based on the results of mating tests, APO penile erection tests, and ICP/MAP measurements. The NO-cGMP pathway alterations and penile fibrosis levels were estimated using Western blotting and Masson staining. Results: (1) The APO penile erection assay, mating experiment, and biological signs demonstrated that starting in the fourth week, the rats in the modeling group had significantly higher core temperatures, fecal output, food intake, water intake, and urine output when compared to control group rats. The latency to mounting, penetration, and ejaculation was greater, and the number of mounting, penetration, and ejaculation events was significantly lower. Both the erection delay and the frequency of erections were significantly decreased. During weeks two and three, rats in group Y exhibited considerably decreased diet, urine volume, and core temperature, but significantly higher body weight, water consumption, and stool volume. The latency to mounting, penetration, and ejaculation was shorter, and the number of mounting, penetration, and ejaculation events was significantly higher. According to the APO experiment's results, the Y group experienced considerably more erections and a significantly shorter erectile delay in the first, second, and third weeks than the ED group. (2) Serum TG, TC, LDL-C, and HDL-C values were considerably higher in groups S and ED than in group N; following medication administration, these indices were significantly lower in group Y. (3) The hemorheological indices (whole-blood high tangent, whole-blood middle tangent, and whole-blood low tangent) in groups S, ED, and Y, and erythrocyte pressure area in group ED, were significantly higher compared to their corresponding values in group N. After the drug was administered, the rheological indices (whole-blood high cut, whole-blood middle cut, whole-blood low cut, and erythrocyte pressure area) were significantly lower in group Y than in group ED. (4) All other groups had higher serum levels of ET-1 than the normal group but without statistically significant differences. The ED group's serum NO content was significantly lower than that of the N group. The serum NO content in the Y group increased after drug intervention. (5) Group S had a significantly decreased ICP/MAP ratio than groups N and ED. Following drug administration, group Y's ICP/MAP ratio was significantly greater compared to that of group ED (p < 0.05); (6) Group S had a lower myofibrillar fiber/collagen fiber ratio than group N, and following drug treatment, group Y exhibited a lower myofibrillar fiber/collagen fiber ratio than group ED (p < 0.05). Compared to group Y, the myofibrillar/collagen fiber ratio in group Y was significantly greater. (7) The expression of nNOS, eNOS, and cGMP followed the order group S < group N < group ED and all differences increased significantly after drug intervention. Conclusion: (1) We exposed rats to a cold environment and administered a high-fat diet to establish a rat model of CCPTBS. Its biological characteristics were highly compatible with the clinical manifestations of blood stasis syndrome. (2) CCPTBS decreased sexual behavior and penile erection in rats that ultimately developed ED. The modeling rate was 59.09%, and the models were suitable and compatible with the clinical manifestations. (3) Our results showed that fibrosis of penile smooth muscle tissue and alteration of blood rheology are associated with ED, and Yimusake tablets can be used for treating ED in rats.